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History of Changes for Study: NCT02420821
A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma (RCC) (IMmotion151)
Latest version (submitted January 4, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 April 15, 2015 None (earliest Version on record)
2 May 11, 2015 Recruitment Status, Contacts/Locations and Study Status
3 May 29, 2015 Contacts/Locations and Study Status
4 June 1, 2015 Study Status
5 September 14, 2015 Contacts/Locations, Arms and Interventions, Study Status, Eligibility, Outcome Measures, Study Description and Study Identification
6 September 17, 2015 Contacts/Locations, Study Status and Study Identification
7 October 1, 2015 Contacts/Locations and Study Status
8 November 2, 2015 Contacts/Locations and Study Status
9 December 1, 2015 Contacts/Locations and Study Status
10 December 31, 2015 Contacts/Locations, Study Design and Study Status
11 February 11, 2016 Outcome Measures, Contacts/Locations, Arms and Interventions, Study Status, Study Identification, Eligibility and Study Description
12 March 1, 2016 Contacts/Locations and Study Status
13 April 2, 2016 Contacts/Locations and Study Status
14 May 4, 2016 Contacts/Locations and Study Status
15 June 1, 2016 Contacts/Locations and Study Status
16 July 1, 2016 Study Status, Contacts/Locations and Study Design
17 August 1, 2016 Contacts/Locations and Study Status
18 August 15, 2016 Contacts/Locations, Arms and Interventions and Study Status
19 September 1, 2016 Contacts/Locations and Study Status
20 October 3, 2016 Contacts/Locations and Study Status
21 November 1, 2016 Contacts/Locations and Study Status
22 February 28, 2017 Recruitment Status, Contacts/Locations, Arms and Interventions, Outcome Measures, Study Status, Study Design, Study Identification, Eligibility and Study Description
23 April 5, 2017 Study Status and Contacts/Locations
24 May 5, 2017 Contacts/Locations and Study Status
25 July 13, 2017 Contacts/Locations and Study Status
26 August 1, 2017 Study Status
27 January 8, 2018 Contacts/Locations and Study Status
28 January 12, 2018 Study Status
29 January 17, 2018 Study Status
30 February 28, 2018 Recruitment Status, Contacts/Locations, Study Status and Study Design
31 March 14, 2018 Recruitment Status, Study Status, Contacts/Locations and Study Design
32 April 2, 2018 Study Status and Contacts/Locations
33 April 23, 2018 Study Status
34 May 7, 2018 Study Status
35 June 4, 2018 Study Status
36 June 18, 2018 Study Status and Contacts/Locations
37 June 26, 2018 Study Status
38 July 30, 2018 Outcome Measures, Arms and Interventions, Study Status, Study Identification, Contacts/Locations, Eligibility and Study Description
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Results Submission Events
39 September 4, 2018 Study Status, Outcome Measures, Contacts/Locations, Document Section and Results
40 November 26, 2018 Study Status
41 February 18, 2019 Study Status and Contacts/Locations
42 February 21, 2019 Study Status
43 May 13, 2019 Study Status and Contacts/Locations
44 August 5, 2019 Contacts/Locations and Study Status
45 September 9, 2019 Study Status and Contacts/Locations
46 September 16, 2019 Study Status
47 October 14, 2019 Study Status and Contacts/Locations
48 October 22, 2019 Contacts/Locations and Study Status
49 January 13, 2020 Study Status and Contacts/Locations
50 March 4, 2020 Study Status and Contacts/Locations
51 May 26, 2020 Contacts/Locations and Study Status
52 August 17, 2020 Contacts/Locations and Study Status
53 September 14, 2020 Study Status and Contacts/Locations
54 October 13, 2020 Study Status
55 January 20, 2021 Contacts/Locations and Study Status
56 March 18, 2021 Study Status and Contacts/Locations
57 May 6, 2021 Study Status
58 July 27, 2021 Study Status and Contacts/Locations
59 October 19, 2021 Contacts/Locations and Study Status
60 January 13, 2022 Recruitment Status, Study Status and Contacts/Locations
61 January 4, 2023 Adverse Events, Outcome Measures, Participant Flow, Study Status, Contacts/Locations and More Information
Comparison Format:
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Study NCT02420821
Submitted Date:  January 13, 2020 (v49)
Open or close this module Study Identification
Unique Protocol ID: WO29637
Brief Title: A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma (RCC) (IMmotion151)
Official Title: A Phase III, Open-Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma
Secondary IDs: 2014-004684-20 [EudraCT Number]
Open or close this module Study Status
Record Verification: January 2020
Overall Status: Active, not recruiting
Study Start: May 20, 2015
Primary Completion: September 29, 2017 [Actual]
Study Completion: December 1, 2021 [Anticipated]
First Submitted: April 15, 2015
First Submitted that
Met QC Criteria:		 April 15, 2015
First Posted: April 20, 2015 [Estimate]
Results First Submitted: August 21, 2018
Results First Submitted that
Met QC Criteria:		 September 4, 2018
Results First Posted: October 3, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:		 January 13, 2020
Last Update Posted: January 18, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Hoffmann-La Roche
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring:
Open or close this module Study Description
Brief Summary: This multi-center, randomized, open-label study will evaluate the efficacy and safety of atezolizumab plus bevacizumab versus sunitinib in participants with inoperable, locally advanced, or metastatic RCC who have not received prior systemic active or experimental therapy, either in the adjuvant or metastatic setting.
Detailed Description:
Open or close this module Conditions
Conditions: Renal Cell Carcinoma
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 915 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Atezolizumab + Bevacizumab
Participants will receive both atezolizumab and bevacizumab until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.
 Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Days 1 and 22 of each 42-day cycle.
Other Names:
  • Tecentriq, MPDL3280A
Drug: Bevacizumab
Bevacizumab will be administered at a dose of 15 milligrams per kilogram (mg/kg) via IV infusion on Days 1 and 22 of each 42-day cycle.
Other Names:
  • Avastin
Active Comparator: Sunitinib
Participants will receive sunitinib until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.
 Drug: Sunitinib
Sunitinib will be administered at a dose of 50 mg once daily, orally via capsule, on Day 1 through Day 28 of each 42-day cycle.
Other Names:
  • Sutent
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. Percentage of Participants With Disease Progression as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death From Any Cause in Programmed Death-Ligand 1 (PD-L1)-Selected Population
[ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

Tumor response was assessed by the investigator according to RECIST v1.1. Disease Progression (PD) was defined as greater than or equal to (>/=) 20 percent (%) relative increase in the sum of diameters (SoD) of all target lesions (TLs), taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 millimeters (mm); >/=1 new lesion(s); and/or unequivocal progression of existing non-TLs.
2. Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 in PD-L1-Selected Population
[ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed >/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% confidence interval (CI) was assessed using the method of Brookmeyer and Crowley.
3. Percentage of Participants Who Died of Any Cause in ITT Population
[ Time Frame: Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months) ]

Percentage of participants who died of any cause was reported.
4. Overall Survival (OS) in ITT Population
[ Time Frame: Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months) ]

OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Secondary Outcome Measures:
1. Percentage of Participants Who Died of Any Cause in PD-L1-Selected Population
[ Time Frame: Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months) ]

Percentage of participants who died of any cause was reported.
2. OS in PD-L1-Selected Population
[ Time Frame: Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months) ]

OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
3. Percentage of Participants With PD as Determined by an Independent Review Committee (IRC) According to RECIST v1.1 or Death From Any Cause in ITT Population
[ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
4. PFS as Determined by an IRC According to RECIST v1.1 in ITT Population
[ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
5. Percentage of Participants With PD as Determined by an IRC According to RECIST v1.1 or Death From Any Cause in PD-L1-Selected Population
[ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
6. PFS as Determined by an IRC According to RECIST v1.1 in PD-L1-Selected Population
[ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
7. Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator According to RECIST v1.1 in Objective Response Rate (ORR)-Evaluable Population
[ Time Frame: Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

Tumor response was assessed by the investigator according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to less than (<) 10 mm. PR was defined as >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.
8. Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 in DOR-Evaluable Population
[ Time Frame: Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.
9. Percentage of Participants With an Objective Response of CR or PR as Determined by an IRC According to RECIST v1.1 in ORR-Evaluable Population
[ Time Frame: Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

Tumor response was assessed by an IRC according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR was defined as >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.
10. DOR as Determined by an IRC According to RECIST v1.1 in DOR-Evaluable Population
[ Time Frame: Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

DOR was defined as the time from the first occurrence of CR/PR to PD as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.
11. Percentage of Participants With PD as Determined by the Investigator According to Immune-Modified RECIST or Death From Any Cause in ITT Population
[ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

Tumor response was assessed by the investigator according to immune-modified RECIST. PD was defined as >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm.
12. PFS as Determined by the Investigator According to Immune-Modified RECIST in ITT Population
[ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

PFS was defined as the time from randomization to PD, as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
13. Percentage of Participants With an Objective Response of CR or PR as Determined by the Investigator According to Immune-Modified RECIST in ORR-Evaluable Population
[ Time Frame: Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

Tumor response was assessed by the investigator according to immune-modified RECIST. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs or reduction in short axis of any pathological lymph nodes to <10 mm. PR was defined as >/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.
14. DOR as Determined by the Investigator According to Immune-Modified RECIST in DOR-Evaluable Population
[ Time Frame: Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. PD: >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.
15. Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in ITT Population
[ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
16. PFS as Determined by the Investigator According to RECIST v1.1 in ITT Population
[ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed >/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
17. Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in Participants With Sarcomatoid Histology
[ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
18. PFS as Determined by the Investigator According to RECIST v1.1 in Participants With Sarcomatoid Histology
[ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]

PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
19. Percentage of Participants Who Died of Any Cause in Participants With Sarcomatoid Histology
[ Time Frame: Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months) ]

Percentage of participants who died of any cause was reported.
20. OS in Participants With Sarcomatoid Histology
[ Time Frame: Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months) ]

OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
21. Change From Baseline in Symptom Interference as Determined by M.D. Anderson Symptom Inventory (MDASI) Part II Score
[ Time Frame: Baseline (Day 1 Cycle 1); Day 22 Cycle 1; Day 1 and 22 of every cycle from Cycle 2 up to Cycle 19; Cycle length = 42 days ]

The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part II, participants were asked to rate how much the symptoms have interfered with 6 areas of function (general activity, walking, work, mood, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely) and total Part II score was calculated as an average of 6-item scores. Repeated measures model-estimated least-squares (LS) mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement. Here, 'Number Analyzed' = number of participants evaluable at specified time point.
22. Change From Baseline in Symptom Severity as Determined by MDASI Part I Score
[ Time Frame: Baseline; End of Treatment (EoT) visit (up to approximately 27 months) ]

The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part I, participants were asked to rate how severe the symptoms (pain, fatigue, nausea, disturbed sleep, feeling of being distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, feeling sad, vomiting, numbness or tingling, rash/skin changes, headache, mouth/throat sores, and diarrhea) were when "at their worst" in the last 24 hours. Each item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Mixed-effects model-estimated LS mean score for change from baseline at the end-of treatment is reported for each item, where a negative value indicates improvement.
23. Change From Baseline in Symptom Severity as Determined by Brief Fatigue Inventory (BFI) Interference Scale Score
[ Time Frame: Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days ]

The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI interference subscale (6 items) assessed the impact of fatigue on global domains (general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely). Change from baseline in the mean score of all 6 items at each timepoint is reported, where a negative value indicates improvement.
24. Change From Baseline in Symptom Severity as Determined by BFI Worst Fatigue Item
[ Time Frame: Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days ]

The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI worst fatigue item assessed the severity of fatigue at its worst in the last 24 hours. The item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Change from baseline in the score at each time point is reported, where a negative value indicates improvement.
25. Change From Baseline in Treatment Side Effects Burden as Determined by Functional Assessment of Cancer Therapy Kidney Symptom Index (FKSI-19) General Population 5 (GP5) Item Score
[ Time Frame: Day 1 and 22 of every cycle (Baseline = Day 1 Cycle 1) up to Cycle 19; Cycle length = 42 days ]

The FKSI-19 is a 19-item tool designed to assess the most important symptoms and concerns related to treatment effectiveness in advanced kidney cancer. The FKSI-19 GP5 item (bothered by the side effect of treatment) assessed side effects burden in the past 7 days on a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Repeated measures model-estimated LS mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement.
26. Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab
[ Time Frame: Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycles 2, 4, and 8, and every eight cycles thereafter up to EoT [up to approximately 27 months] and 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days) ]

The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against atezolizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result. Here, 'Overall Number of Participants Analyzed' = number of participants with a non-missing baseline ATA sample; 'Number Analyzed' = number of participants with a non-missing ATA sample at indicated timepoint.
27. Number of Participants With ATAs Against Bevacizumab
[ Time Frame: Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycle 3, at EoT [up to approximately 27 months] and at 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days) ]

The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against bevacizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result.
28. Maximum Observed Serum Concentration (Cmax) for Atezolizumab
[ Time Frame: 30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days) ]

Cmax for atezolizumab was estimated from plasma concentration versus time data.
29. Minimum Observed Serum Concentration (Cmin) for Atezolizumab
[ Time Frame: Predose (Hour 0) on Day 22 of Cycle 1; predose (Hour 0) on Day 1 of Cycles 2; Cycle length = 42 days ]

Cmin for atezolizumab was estimated from plasma concentration versus time data.
30. Cmax for Bevacizumab
[ Time Frame: 30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days) ]

Cmax for bevacizumab was estimated from plasma concentration versus time data.
31. Cmin for Bevacizumab
[ Time Frame: Pre-dose (Hour 0) on Day 1 of Cycle 3 (Cycle length = 42 days) ]

Cmin for bevacizumab was estimated from plasma concentration versus time data.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Definitive diagnosis of unresectable locally advanced or metastatic RCC with clear-cell histology and/or a component of sarcomatoid carcinoma, with no prior treatment in the metastatic setting
  • Evaluable Memorial Sloan Kettering Cancer Center risk score
  • Measurable disease, as defined by RECIST v1.1
  • Karnofsky performance status greater than or equal to 70%
  • Adequate hematologic and end-organ function prior to randomization

Exclusion Criteria:

Disease-Specific Exclusions:

  • Radiotherapy for RCC within 14 days prior to treatment
  • Active central nervous system disease
  • Uncontrolled pleural effusion, pericardial effusion, or ascites
  • Uncontrolled hypercalcemia
  • Any other malignancies within 5 years except for low-risk prostate cancer or those with negligible risk of metastasis or death

General Medical Exclusions:

  • Life expectancy less than 12 weeks
  • Participation in another experimental drug study within 4 weeks prior to treatment
  • Pregnant or lactating women
  • Known hypersensitivity to any component of atezolizumab or other study medication
  • History of autoimmune disease except controlled, treated hypothyroidism or type I diabetes mellitus
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis
  • Positive human immunodeficiency virus test
  • Active or chronic hepatitis B or C
  • Severe infections within 4 weeks prior to treatment
  • Exposure to oral or IV antibiotics within 2 weeks prior to treatment
  • Live attenuated vaccines within 4 weeks prior to treatment (for influenza vaccination participants must agree not to receive live, attenuated influenza vaccine within 4 weeks prior to treatment, during treatment or within 5 months following the last dose)
  • Significant cardiovascular disease
  • Prior allogeneic stem cell or solid organ transplantation

Exclusion Criteria Related to Medications:

  • Prior treatment with cluster of differentiation 137 agonists, anti-cytotoxic T-lymphocyte associated protein-4, anti-programmed death (PD)-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
  • Treatment with immunostimulatory agents for non-malignant conditions within 6 weeks or immunosuppressive agents within 2 weeks prior to treatment

Bevacizumab- and Sunitinib-Specific Exclusions:

  • History of hypertensive crisis or hypertensive encephalopathy
  • Baseline electrocardiogram showing corrected QT interval greater than 460 milliseconds
Open or close this module Contacts/Locations
Study Officials: Clinical Trials
Study Director
Hoffmann-La Roche
Locations: United States, Arizona
University of Arizona Cancer Center
Tucson, Arizona, United States, 85719
United States, California
University of California at Irvine Medical Center; Department of Oncology
Orange, California, United States, 92868
University of California
San Francisco, California, United States, 94158
United States, Colorado
University of Colorado; Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
Rocky Mountain Cancer Center; Medical Oncology
Denver, Colorado, United States, 80218
United States, District of Columbia
Georgetown U; Lombardi Comp Can
Washington, District of Columbia, United States, 20016-1468
United States, Florida
Lynn Cancer Institute/Boca Raton Regional Hospital
Boca Raton, Florida, United States, 33486
Florida Cancer Specialists - Port Charlotte
Port Charlotte, Florida, United States, 33980
Florida Cancer Specialist, North Region
Saint Petersburg, Florida, United States, 33705
United States, Georgia
Piedmont Cancer Institute, PC
Atlanta, Georgia, United States, 30318
United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
United States, Kentucky
Norton Cancer Institute
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Inst.
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Nevada
Comprehensive Cancer Centers of Nevada - Eastern Avenue
Las Vegas, Nevada, United States, 89169
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
New York Oncology Hematology,P.C.-Albany
Albany, New York, United States, 12208
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
Oncology Hematology Care Inc
Cincinnati, Ohio, United States, 45242
Cleveland Clinic Foundation; Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Oregon
Northwest Cancer Specialists, P.C.
Tigard, Oregon, United States, 97223
United States, Tennessee
SCRI Tennessee Oncology Chattanooga
Chattanooga, Tennessee, United States, 37404
Sarah Cannon Cancer Center and Research Institute
Nashville, Tennessee, United States, 37203
Vanderbilt Univ Medical Ctr
Nashville, Tennessee, United States, 37232
United States, Texas
Texas Oncology-Baylor Sammons Cancer Center
Dallas, Texas, United States, 75246
United States, Virginia
Oncology and Hematology Associates of SW Virginia-Raonoke
Roanoke, Virginia, United States, 24014
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Australia, New South Wales
Lifehouse
Camperdown, New South Wales, Australia, 2050
Macquarie University Hospital
Sydney, New South Wales, Australia, 2109
Calvary Mater Newcastle; Medical Oncology
Waratah, New South Wales, Australia, 2298
Australia, Queensland
Icon Cancer Foundation
South Brisbane, Queensland, Australia, 4101
Australia, South Australia
Ashford Cancer Center Research
Kurralta Park, South Australia, Australia, 5037
Australia, Victoria
Austin Hospital; Medical Oncology
Heidelberg, Victoria, Australia, 3084
Australia, Western Australia
St John of God Hospital
Murdoch, Western Australia, Australia, WA6150
Bosnia and Herzegovina
University Clinical Centre of the Republic of Srpska
Banja Luka, Bosnia and Herzegovina, 78000
Brazil, RS
Hospital de Caridade de Ijui; Oncologia
Ijui, RS, Brazil, 98700-000
Santa Casa de Misericordia de Porto Alegre
Porto Alegre, RS, Brazil, 90020-090
Hospital Sao Lucas - PUCRS
Porto Alegre, RS, Brazil, 90610-000
Brazil, SP
Instituto do Cancer do Estado de Sao Paulo - ICESP
Sao Paulo, SP, Brazil, 01246-000
Canada
Centre Hospitalier universitaire de Québec/ Hotel Dieu de Québec
Quebec, Canada, G1R 3S1
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre; Oncology
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
Royal Victoria Hospital
Barrie, Ontario, Canada, L4M 6M2
Hamilton Health Sciences - Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
London Regional Cancer Centre
London, Ontario, Canada, N6A 4L6
Lakeridge Health Oshawa; Oncology
Oshawa, Ontario, Canada, L1G 2B9
The Ottawa Hospital Cancer Centre; Oncology
Ottawa, Ontario, Canada, K1H 8L6
Sunnybrook Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
Montreal, Quebec, Canada, H3T 1E2
Czechia
Masarykuv onkologicky ustav
Brno, Czechia, 656 53
Fakultni nemocnice Olomouc; Onkologicka klinika
Olomouc, Czechia, 779 00
Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika
Praha 2, Czechia, 128 08
Thomayerova nemocnice
Praha 4 - Krc, Czechia, 140 59
Denmark
Aarhus Universitetshospital; Kræftafdelingen
Aarhus N, Denmark, 8200
Herlev Hospital; Afdeling for Kræftbehandling
Herlev, Denmark, 2730
Odense Universitetshospital, Onkologisk Afdeling R
Odense C, Denmark, 5000
France
ICO Paul Papin; Oncologie Medicale.
Angers, France, 49055
Hopital Saint Andre; Oncologie 2
Bordeaux, France, 33075
Centre Francois Baclesse; Urologie Gynecologie
Caen, France, 14076
Centre Oscar Lambret
Lille, France, 59020
Centre Léon Bérard
Lyon, France, 69373
Institut Paoli Calmettes; Oncologie Medicale
Marseille, France, 13273
Centre D'Oncologie de Gentilly; Oncology
Nancy, France, 54100
APHP - Hospital Saint Louis
Paris, France, 75475
Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale
Paris, France, 75908
ICO - Site René Gauducheau
Saint Herblain, France, 44805
Institut Gustave Roussy; Departement Oncologie Medicale
Villejuif, France, 94805
Germany
Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Urologie
Dresden, Germany, 01307
Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung
Essen, Germany, 45122
Nationales Centrum für Tumorerkrankungen Heidelberg (NCT); Thoraxklinik Heidelberg
Heidelberg, Germany, 69120
Klinikum d.Universität München Campus Großhadern
München, Germany, 81377
Universitätsklinikum Tübingen; Klinik für Urologie
Tübingen, Germany, 72076
Italy, Campania
Az. Osp. Cardarelli; Divisione Di Oncologia
Napoli, Campania, Italy, 80131
Italy, Emilia-Romagna
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
Meldola, Emilia-Romagna, Italy, 47014
A.O. Universitaria Policlinico Di Modena; Oncologia
Modena, Emilia-Romagna, Italy, 41100
Italy, Lazio
Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica
Roma, Lazio, Italy, 00152
Italy, Lombardia
Irccs Ospedale San Raffaele;Oncologia Medica
Milano, Lombardia, Italy, 20132
Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
Milano, Lombardia, Italy, 20162
Fondazione IRCCS Policlinico San Matteo, Oncologia
Pavia, Lombardia, Italy, 27100
Italy, Toscana
Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia
Arezzo, Toscana, Italy, 52100
Japan
Nagoya University Hospital; Urology
Aichi, Japan, 466-8560
Chiba Cancer Center
Chiba, Japan, 260-8717
Kyushu University Hospital
Fukuoka, Japan, 812-8582
Gunma University Hospital
Gunma, Japan, 371-8511
Hokkaido University Hospital
Hokkaido, Japan, 060-8648
University of Tsukuba Hospital; Urology
Ibaraki, Japan, 305-8576
Iwate Medical University Hospital
Iwate, Japan, 028-3695
Yokohama City University Hospital
Kanagawa, Japan, 236-0004
Kitasato University Hospital
Kanagawa, Japan, 252-0375
Kumamoto University Hospital
Kumamoto, Japan, 860-8556
Niigata University Medical & Dental Hospital
Niigata, Japan, 951-8520
Okayama University Hospital
Okayama, Japan, 700-8558
Osaka International Cancer Institute; Urology
Osaka, Japan, 541-8567
Osaka City University Hospital
Osaka, Japan, 545-8586
Osaka University Hospital
Osaka, Japan, 565-0871
Kindai University Hospital
Osaka, Japan, 589-8511
Tokushima University Hospital
Tokushima, Japan, 770-8503
Toranomon Hospital
Tokyo, Japan, 105-8470
Tokyo Medical & Dental University Hospital
Tokyo, Japan, 113-8519
Nippon Medical School Hospital
Tokyo, Japan, 113-8603
The Cancer Institute Hospital, JFCR; Urology
Tokyo, Japan, 135-8550
Keio University Hospital
Tokyo, Japan, 160-8582
Tokyo Women's Medical University
Tokyo, Japan, 162-0054
Korea, Republic of
Chungnam National University Hospital
Daejeon, Korea, Republic of, 35015
National Cancer Center
Gyeonggi-do, Korea, Republic of, 10408
Seoul National University Bundang Hospital
Gyeonggi-do, Korea, Republic of, 13620
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Severance Hospital, Yonsei University Health System
Seoul, Korea, Republic of, 03722
Asan Medical Center - Oncology
Seoul, Korea, Republic of, 05505
Samsung Medical Center
Seoul, Korea, Republic of, 06351
Mexico
Cancerología
Queretaro, Mexico, 76090
Centro Oncologico Estatal ISSEMYM
Toluca, Mexico, 50180
Poland
Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli
Lublin, Poland, 20-090
Szpital Kliniczny; Przemienienia Panskiego;Uniwersytetu Medyczny im.; Karola Marcinkowskiego w Pozna
Poznan, Poland, 60-569
Saint Elizabeth's Hospital
Warsaw, Poland, 02-616
MAGODENT Sp. z o.o.
Warsaw, Poland, 04-125
Russian Federation
P.A. Herzen Oncological Inst. ; Oncology
Moscow, Russian Federation, 125284
Moscow city oncology hospital #62 of Moscow Healthcare Department
Moscow, Russian Federation, 143423
Russian Federation, Altaj
ALTAI REGIONAL ONCOLOGICAL CENTER; "Nadezhda" Clinic
Barnaul, Altaj, Russian Federation, 656049
Russian Federation, Niznij Novgorod
GBUZ Nizhegorodskay Region: Clinical Diagnostic Center
Nizhni Novgorod, Niznij Novgorod, Russian Federation, 603001
Singapore
National University Hospital
Singapore, Singapore, 119074
National Cancer Centre; Medical Oncology
Singapore, Singapore, 169610
Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, Spain, 08035
Hospital Clínic i Provincial; Servicio de Oncología
Barcelona, Spain, 08036
Hospital Duran i Reynals; Oncologia
Barcelona, Spain, 08907
Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
Madrid, Spain, 28007
Hospital Ramon y Cajal; Servicio de Oncologia
Madrid, Spain, 28034
Hospital Universitario 12 de Octubre; Servicio de Oncologia
Madrid, Spain, 28041
Hospital Universitario Virgen del Rocio; Servicio de Oncologia
Sevilla, Spain, 41013
Spain, Barcelona
Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
Sabadell, Barcelona, Spain, 08208
Spain, Cordoba
Hospital Universitario Reina Sofia; Servicio de Oncologia
Córdoba, Cordoba, Spain, 14004
Taiwan
Taichung Veterans General Hospital; Division of Urology
Taichung, Taiwan, 407
National Taiwan Uni Hospital; Dept of Oncology
Taipei, Taiwan, 100
Chang Gung Medical Foundation-Linkou, Urinary Oncology
Taoyuan, Taiwan, 333
Thailand
Chulalongkorn Hospital; Medical Oncology
Bangkok, Thailand, 10330
Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
Bangkok, Thailand, 10400
Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
Bangkok, Thailand, 10700
Maharaj Nakorn Chiangmai Hospital; Department of Surgery/ Urology unit
Chiangmai, Thailand, 50200
Songklanagarind Hospital; Department of Oncology
Songkhla, Thailand, 90110
Turkey
Hacettepe University Medical Faculty
Ankara, Turkey, 06100
Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department
Edirne, Turkey, 22770
Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology
Istanbul, Turkey, 34300
United Kingdom
Clatterbridge Cancer Centre
Bebington, United Kingdom, CH63 4JY
Queen Elizabeth Hospital
Birmingham, United Kingdom, B15 2TH
Royal Blackburn Hospital
Blackburn, United Kingdom, BB2 3HH
Addenbrookes Nhs Trust; Oncology Clinical Trials Unit
Cambridge, United Kingdom, CB2 0QQ
Barts Health NHS Trust - St Bartholomew's Hospital
London, United Kingdom, EC1A 7BE
Royal Free Hospital; Dept of Oncology
London, United Kingdom, NW3 2QG
Christie Hospital Nhs Trust; Medical Oncology
Manchester, United Kingdom, M2O 4BX
Churchill Hospital; Oxford Cancer and Haematology Centre
Oxford, United Kingdom, OX3 7LJ
Southampton General Hospital; Medical Oncology
Southampton, United Kingdom, SO16 6YD
Royal Marsden Hospital; Dept of Medical Oncology
Sutton, United Kingdom, SM2 5PT
Singleton Hospital; Pharmacy Department
Swansea, United Kingdom, SA2 8QA
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:
Open or close this module Document Section
Study Protocol and Statistical Analysis Plan
Document Date: April 3, 2018
Uploaded: 08/21/2018 15:36
File Name: Prot_SAP_000.pdf
Study Results
Open or close this module Participant Flow
Recruitment Details
Pre-assignment Details A total of 1228 participants were screened, out of which, 915 participants were enrolled into the study.
 
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Arm/Group Description Participants received sunitinib at a dose of 50 milligrams (mg) administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to disease progression (PD) as determined by the investigator, withdrawal of consent, or death, whichever occurred first. Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 milligrams per kilogram (mg/kg) administered via intravenous (IV) infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Period Title: Overall Study
Started 461 454
Completed 293 317
Not Completed 168 137
Reason Not Completed
Lost to Follow-up 2 0
Non-compliance 1 2
Physician Decision 5 2
Withdrawal by Subject 31 17
Death 129 116
Open or close this module Baseline Characteristics
Arm/Group TitleSunitinibAtezolizumab + BevacizumabTotal
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Total of all reporting groups
Overall Number of Baseline Participants 461 454 915
Baseline Analysis Population Description
Age, Continuous
Mean (Standard Deviation)
Unit of measure: years
Number Analyzed461 Participants454 Participants915 Participants
59.9(9.9)61.6(10.4)60.7(10.2)
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed461 Participants454 Participants915 Participants
Female
109
23.64%
137
30.18%
246
26.89%
Male
352
76.36%
317
69.82%
669
73.11%
Ethnicity (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed461 Participants454 Participants915 Participants
Hispanic or Latino
32
6.94%
25
5.51%
57
6.23%
Not Hispanic or Latino
386
83.73%
391
86.12%
777
84.92%
Unknown or Not Reported
43
9.33%
38
8.37%
81
8.85%
Race (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed461 Participants454 Participants915 Participants
American Indian or Alaska Native
1
0.22%
2
0.44%
3
0.33%
Asian
77
16.7%
94
20.7%
171
18.69%
Native Hawaiian or Other Pacific Islander
0
0%
1
0.22%
1
0.11%
Black or African American
4
0.87%
1
0.22%
5
0.55%
White
334
72.45%
326
71.81%
660
72.13%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
45
9.76%
30
6.61%
75
8.2%
Open or close this module Outcome Measures
1. Primary Outcome:
Title Percentage of Participants With Disease Progression as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death From Any Cause in Programmed Death-Ligand 1 (PD-L1)-Selected Population
Description Tumor response was assessed by the investigator according to RECIST v1.1. Disease Progression (PD) was defined as greater than or equal to (>/=) 20 percent (%) relative increase in the sum of diameters (SoD) of all target lesions (TLs), taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 millimeters (mm); >/=1 new lesion(s); and/or unequivocal progression of existing non-TLs.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the PD-L1-Selected Population, which included all participants in the ITT population whose PD-L1 status was immune cell (IC)1/2/3 at the time of randomization.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed184 178
Measure Type: Number
Unit of Measure: percentage of participants
69.6 58.4
2. Primary Outcome:
Title Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 in PD-L1-Selected Population
Description PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed >/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% confidence interval (CI) was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the PD-L1-Selected Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed184 178
Median (95% Confidence Interval)
Unit of Measure: months
7.5(6.8 to 9.7) 11.2(8.6 to 14.3)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsStratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0205
Comments[Not specified]
MethodLog Rank
Comments[Not specified]
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.73
Confidence Interval(2-sided) 95%
0.57 to 0.95
Estimation CommentsHazard ratio was estimated by Cox regression.
3. Primary Outcome:
Title Percentage of Participants Who Died of Any Cause in ITT Population
Description Percentage of participants who died of any cause was reported.
Time Frame Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ITT Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed461 454
Measure Type: Number
Unit of Measure: percentage of participants
30.6 27.1
4. Primary Outcome:
Title Overall Survival (OS) in ITT Population
Description OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ITT Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed461 454
Median (95% Confidence Interval)
Unit of Measure: months
NA(23.3 to NA) [1] NA(NA to NA) [2]
[1]NA Explanation: Median and upper limit of 95% CI could not be estimated due to high number of censored participants.
[2]NA Explanation: Median and corresponding 95% CI could not be estimated due to high number of censored participants.
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsStratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0895
Comments[Not specified]
MethodLog Rank
Comments[Not specified]
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.81
Confidence Interval(2-sided) 95%
0.63 to 1.03
Estimation CommentsHazard ratio was estimated by Cox regression.
5. Secondary Outcome:
Title Percentage of Participants Who Died of Any Cause in PD-L1-Selected Population
Description Percentage of participants who died of any cause was reported.
Time Frame Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the PD-L1-Selected Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed184 178
Measure Type: Number
Unit of Measure: percentage of participants
34.8 25.3
6. Secondary Outcome:
Title OS in PD-L1-Selected Population
Description OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the PD-L1-Selected Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed184 178
Median (95% Confidence Interval)
Unit of Measure: months
23.3(21.3 to NA) [1] NA(NA to NA) [2]
[1]NA Explanation: Upper limit of 95% CI could not be estimated due to high number of censored participants.
[2]NA Explanation: Median and corresponding 95% CI could not be estimated due to high number of censored participants.
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsStratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0470
Comments[Not specified]
MethodLog Rank
Comments[Not specified]
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.68
Confidence Interval(2-sided) 95%
0.46 to 1.00
Estimation CommentsHazard ratio was estimated by Cox regression.
7. Secondary Outcome:
Title Percentage of Participants With PD as Determined by an Independent Review Committee (IRC) According to RECIST v1.1 or Death From Any Cause in ITT Population
Description Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ITT Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed461 454
Measure Type: Number
Unit of Measure: percentage of participants
63.6 60.4
8. Secondary Outcome:
Title PFS as Determined by an IRC According to RECIST v1.1 in ITT Population
Description PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ITT Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed461 454
Median (95% Confidence Interval)
Unit of Measure: months
8.3(7.0 to 9.7) 9.6(8.3 to 11.5)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsStratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.1218
Comments[Not specified]
MethodLog Rank
Comments[Not specified]
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.88
Confidence Interval(2-sided) 95%
0.74 to 1.04
Estimation CommentsHazard ratio was estimated by Cox regression.
9. Secondary Outcome:
Title Percentage of Participants With PD as Determined by an IRC According to RECIST v1.1 or Death From Any Cause in PD-L1-Selected Population
Description Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the PD-L1-Selected Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed184 178
Measure Type: Number
Unit of Measure: percentage of participants
64.7 62.9
10. Secondary Outcome:
Title PFS as Determined by an IRC According to RECIST v1.1 in PD-L1-Selected Population
Description PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the PD-L1-Selected Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed184 178
Median (95% Confidence Interval)
Unit of Measure: months
7.2(6.1 to 11.1) 8.9(6.9 to 12.5)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsStratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.6138
Comments[Not specified]
MethodLog Rank
Comments[Not specified]
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.93
Confidence Interval(2-sided) 95%
0.72 to 1.21
Estimation CommentsHazard ratio was estimated by Cox regression.
11. Secondary Outcome:
Title Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator According to RECIST v1.1 in Objective Response Rate (ORR)-Evaluable Population
Description Tumor response was assessed by the investigator according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to less than (<) 10 mm. PR was defined as >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.
Time Frame Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ORR-Evaluable Population, which included all participants in the ITT population with measurable disease at baseline, as determined by the investigator.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed460 454
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33.3(28.97 to 37.77) 36.6(32.12 to 41.18)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsStratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.2733
Comments[Not specified]
MethodCochran-Mantel-Haenszel
Comments[Not specified]
Method of EstimationEstimation ParameterDifference in Response Rates
Estimated Value3.30
Confidence Interval(2-sided) 95%
-3.09 to 9.70
Estimation Comments95% CI for difference in response rates was constructed using Wald method.
12. Secondary Outcome:
Title Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 in DOR-Evaluable Population
Description DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.
Time Frame Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on DOR-Evaluable Population, which included all participants with a CR/PR in the ORR-Evaluable Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed153 166
Median (95% Confidence Interval)
Unit of Measure: months
14.2(11.3 to NA) [1] 16.6(15.4 to NA) [1]
[1]NA Explanation: Upper limit of 95% CI could not be estimated due to high number of censored participants.
13. Secondary Outcome:
Title Percentage of Participants With an Objective Response of CR or PR as Determined by an IRC According to RECIST v1.1 in ORR-Evaluable Population
Description Tumor response was assessed by an IRC according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR was defined as >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.
Time Frame Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ORR-Evaluable Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed460 454
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
31.3(27.09 to 35.76) 33.3(28.94 to 37.80)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsStratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.5121
Comments[Not specified]
MethodCochran-Mantel-Haenszel
Comments[Not specified]
Method of EstimationEstimation ParameterDifference in Response Rates
Estimated Value1.96
Confidence Interval(2-sided) 95%
-4.32 to 8.24
Estimation Comments95% CI for difference in response rates was constructed using Wald method.
14. Secondary Outcome:
Title DOR as Determined by an IRC According to RECIST v1.1 in DOR-Evaluable Population
Description DOR was defined as the time from the first occurrence of CR/PR to PD as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.
Time Frame Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the DOR-Evaluable Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed144 151
Median (95% Confidence Interval)
Unit of Measure: months
18.6(13.8 to NA) [1] NA(16.8 to NA) [2]
[1]NA Explanation: Upper limit of 95% CI could not be estimated due to high number of censored participants.
[2]NA Explanation: Median and Upper limit of 95% CI could not be estimated due to high number of censored participants.
15. Secondary Outcome:
Title Percentage of Participants With PD as Determined by the Investigator According to Immune-Modified RECIST or Death From Any Cause in ITT Population
Description Tumor response was assessed by the investigator according to immune-modified RECIST. PD was defined as >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ITT Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed461 454
Measure Type: Number
Unit of Measure: percentage of participants
58.1 55.1
16. Secondary Outcome:
Title PFS as Determined by the Investigator According to Immune-Modified RECIST in ITT Population
Description PFS was defined as the time from randomization to PD, as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ITT Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed461 454
Median (95% Confidence Interval)
Unit of Measure: months
12.3(9.8 to 13.7) 13.9(12.5 to 15.3)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsStratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0606
Comments[Not specified]
MethodLog Rank
Comments[Not specified]
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.85
Confidence Interval(2-sided) 95%
0.71 to 1.01
Estimation CommentsHazard ratio was estimated by Cox regression.
17. Secondary Outcome:
Title Percentage of Participants With an Objective Response of CR or PR as Determined by the Investigator According to Immune-Modified RECIST in ORR-Evaluable Population
Description Tumor response was assessed by the investigator according to immune-modified RECIST. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs or reduction in short axis of any pathological lymph nodes to <10 mm. PR was defined as >/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.
Time Frame Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ORR-Evaluable Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed460 454
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
35.0(30.64 to 39.55) 40.1(35.55 to 44.76)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsStratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.1011
Comments[Not specified]
MethodCochran-Mantel-Haenszel
Comments[Not specified]
Method of EstimationEstimation ParameterDifference in Response Rates
Estimated Value5.09
Confidence Interval(2-sided) 95%
-1.40 to 11.58
Estimation Comments95% CI for difference in response rates was constructed using Wald method.
18. Secondary Outcome:
Title DOR as Determined by the Investigator According to Immune-Modified RECIST in DOR-Evaluable Population
Description DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. PD: >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.
Time Frame Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on DOR-Evaluable Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed161 182
Median (95% Confidence Interval)
Unit of Measure: months
19.4(13.1 to 20.0) 19.4(16.5 to NA) [1]
[1]NA Explanation: Upper limit of 95% CI could not be estimated due to high number of censored participants.
19. Secondary Outcome:
Title Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in ITT Population
Description Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ITT Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed461 454
Measure Type: Number
Unit of Measure: percentage of participants
63.8 60.1
20. Secondary Outcome:
Title PFS as Determined by the Investigator According to RECIST v1.1 in ITT Population
Description PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed >/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ITT Population.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed461 454
Median (95% Confidence Interval)
Unit of Measure: months
8.4(7.5 to 9.7) 11.2(9.6 to 13.6)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsStratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0254
Comments[Not specified]
MethodLog Rank
Comments[Not specified]
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.83
Confidence Interval(2-sided) 95%
0.70 to 0.98
Estimation CommentsHazard ratio was estimated by Cox regression.
21. Secondary Outcome:
Title Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in Participants With Sarcomatoid Histology
Description Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ITT Population participants with sarcomatoid histology (defined by investigator-assessed conventional histopathology).
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed74 68
Measure Type: Number
Unit of Measure: percentage of participants
85.1 67.6
22. Secondary Outcome:
Title PFS as Determined by the Investigator According to RECIST v1.1 in Participants With Sarcomatoid Histology
Description PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ITT Population participants with sarcomatoid histology.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed74 68
Median (95% Confidence Interval)
Unit of Measure: months
5.3(3.3 to 6.7) 8.3(5.4 to 12.9)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsStratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0020
Comments[Not specified]
MethodLog Rank
Comments[Not specified]
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.52
Confidence Interval(2-sided) 95%
0.34 to 0.79
Estimation CommentsHazard ratio was estimated by Cox regression.
23. Secondary Outcome:
Title Percentage of Participants Who Died of Any Cause in Participants With Sarcomatoid Histology
Description Percentage of participants who died of any cause was reported.
Time Frame Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ITT Population participants with sarcomatoid histology.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed74 68
Measure Type: Number
Unit of Measure: percentage of participants
50.0 38.2
24. Secondary Outcome:
Title OS in Participants With Sarcomatoid Histology
Description OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ITT Population participants with sarcomatoid histology.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed74 68
Median (95% Confidence Interval)
Unit of Measure: months
15.0(8.7 to NA) [1] NA(18.3 to NA) [2]
[1]NA Explanation: Upper limit of 95% CI could not be estimated due to high number of censored participants.
[2]NA Explanation: Median/upper limit of 95% CI could not be estimated due to high number of censored participants.
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsStratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0323
Comments[Not specified]
MethodLog Rank
Comments[Not specified]
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.56
Confidence Interval(2-sided) 95%
0.32 to 0.96
Estimation CommentsHazard ratio was estimated by Cox regression.
25. Secondary Outcome:
Title Change From Baseline in Symptom Interference as Determined by M.D. Anderson Symptom Inventory (MDASI) Part II Score
Description The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part II, participants were asked to rate how much the symptoms have interfered with 6 areas of function (general activity, walking, work, mood, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely) and total Part II score was calculated as an average of 6-item scores. Repeated measures model-estimated least-squares (LS) mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement. Here, 'Number Analyzed' = number of participants evaluable at specified time point.
Time Frame Baseline (Day 1 Cycle 1); Day 22 Cycle 1; Day 1 and 22 of every cycle from Cycle 2 up to Cycle 19; Cycle length = 42 days
Outcome Measure Data
Analysis Population Description
Analysis was performed on the patient-reported outcome (PRO)-Evaluable Population, which included all participants with a non-missing baseline PRO assessment and >/=1 post-baseline PRO assessment.
   
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed359 373
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
 
Change at Cycle1 Day 22
Number Analyzed Participants Participants
1.28(0.13) 0.54(0.13)
Change at Cycle 2 Day 1
Number Analyzed Participants Participants
0.76(0.13) 0.56(0.13)
Change at Cycle 2 Day 22
Number Analyzed Participants Participants
1.58(0.13) 0.56(0.13)
Change at Cycle 3 Day 1
Number Analyzed Participants Participants
1.05(0.13) 0.53(0.13)
Change at Cycle 3 Day 22
Number Analyzed Participants Participants
1.63(0.14) 0.61(0.13)
Change at Cycle 4 Day 1
Number Analyzed Participants Participants
1.02(0.14) 0.59(0.13)
Change at Cycle 4 Day 22
Number Analyzed Participants Participants
1.55(0.14) 0.57(0.14)
Change at Cycle 5 Day 1
Number Analyzed Participants Participants
1.18(0.15) 0.72(0.14)
Change at Cycle 5 Day 22
Number Analyzed Participants Participants
1.56(0.15) 0.78(0.14)
Change at Cycle 6 Day 1
Number Analyzed Participants Participants
1.03(0.15) 0.82(0.14)
Change at Cycle 6 Day 22
Number Analyzed Participants Participants
1.44(0.15) 0.80(0.15)
Change at Cycle 7 Day 1
Number Analyzed Participants Participants
1.15(0.16) 0.72(0.15)
Change at Cycle 7 Day 22
Number Analyzed Participants Participants
1.43(0.16) 0.66(0.15)
Change at Cycle 8 Day 1
Number Analyzed Participants Participants
1.06(0.16) 0.76(0.15)
Change at Cycle 8 Day 22
Number Analyzed Participants Participants
1.34(0.17) 0.69(0.15)
Change at Cycle 9 Day 1
Number Analyzed Participants Participants
1.05(0.17) 0.67(0.16)
Change at Cycle 9 Day 22
Number Analyzed Participants Participants
1.46(0.18) 0.56(0.16)
Change at Cycle 10 Day 1
Number Analyzed Participants Participants
1.24(0.18) 0.61(0.16)
Change at Cycle 10 Day 22
Number Analyzed Participants Participants
1.61(0.20) 0.60(0.17)
Change at Cycle 11 Day 1
Number Analyzed Participants Participants
1.12(0.19) 0.62(0.17)
Change at Cycle 11 Day 22
Number Analyzed Participants Participants
1.45(0.21) 0.61(0.18)
Change at Cycle 12 Day 1
Number Analyzed Participants Participants
1.02(0.21) 0.53(0.18)
Change at Cycle 12 Day 22
Number Analyzed Participants Participants
1.45(0.24) 0.69(0.20)
Change at Cycle 13 Day 1
Number Analyzed Participants Participants
0.79(0.24) 0.80(0.21)
Change at Cycle 13 Day 22
Number Analyzed Participants Participants
1.09(0.27) 0.73(0.22)
Change at Cycle 14 Day 1
Number Analyzed Participants Participants
0.86(0.27) 0.73(0.24)
Change at Cycle 14 Day 22
Number Analyzed Participants Participants
1.22(0.31) 0.83(0.25)
Change at Cycle 15 Day 1
Number Analyzed Participants Participants
0.93(0.31) 0.78(0.27)
Change at Cycle 15 Day 22
Number Analyzed Participants Participants
1.67(0.37) 0.88(0.29)
Change at Cycle 16 Day 1
Number Analyzed Participants Participants
0.90(0.38) 0.98(0.32)
Change at Cycle 16 Day 22
Number Analyzed Participants Participants
1.30(0.43) 1.32(0.36)
Change at Cycle 17 Day 1
Number Analyzed Participants Participants
0.80(0.46) 1.18(0.40)
Change at Cycle 17 Day 22
Number Analyzed Participants Participants
0.92(0.53) 0.95(0.47)
Change at Cycle 18 Day 1
Number Analyzed Participants Participants
0.75(0.64) 0.75(0.53)
Change at Cycle 18 Day 22
Number Analyzed Participants Participants
0.65(0.86) 0.87(0.63)
Change at Cycle 19 Day 1
Number Analyzed Participants Participants
0.29(1.58) 0.80(0.73)
Change at Cycle 19 Day 22
Number Analyzed Participants Participants
0.88(1.03)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 1 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.74
Confidence Interval(2-sided) 95%
-1.06 to -0.43
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 2
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 2 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.2085
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.20
Confidence Interval(2-sided) 95%
-0.51 to 0.11
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 3
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 2 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-1.02
Confidence Interval(2-sided) 95%
-1.33 to -0.71
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 4
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 3 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0013
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.51
Confidence Interval(2-sided) 95%
-0.82 to -0.20
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 5
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 3 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-1.02
Confidence Interval(2-sided) 95%
-1.34 to -0.70
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 6
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 4 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0098
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.43
Confidence Interval(2-sided) 95%
-0.76 to -0.10
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 7
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 4 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.98
Confidence Interval(2-sided) 95%
-1.32 to -0.65
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 8
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 5 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0080
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.46
Confidence Interval(2-sided) 95%
-0.80 to -0.12
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 9
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 5 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.78
Confidence Interval(2-sided) 95%
-1.13 to -0.44
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 10
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 6 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.2512
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.21
Confidence Interval(2-sided) 95%
-0.56 to 0.15
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 11
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 6 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0005
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.65
Confidence Interval(2-sided) 95%
-1.01 to -0.28
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 12
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 7 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0247
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.43
Confidence Interval(2-sided) 95%
-0.80 to -0.05
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 13
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 7 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.77
Confidence Interval(2-sided) 95%
-1.15 to -0.39
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 14
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 8 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.1411
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.29
Confidence Interval(2-sided) 95%
-0.68 to 0.10
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 15
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 8 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0014
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.65
Confidence Interval(2-sided) 95%
-1.05 to -0.25
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 16
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 9 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0728
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.37
Confidence Interval(2-sided) 95%
-0.78 to 0.03
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 17
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 9 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.90
Confidence Interval(2-sided) 95%
-1.32 to -0.49
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 18
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 10 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0041
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.62
Confidence Interval(2-sided) 95%
-1.05 to -0.20
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 19
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 10 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-1.00
Confidence Interval(2-sided) 95%
-1.46 to -0.55
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 20
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 11 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0353
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.50
Confidence Interval(2-sided) 95%
-0.96 to -0.03
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 21
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 11 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0011
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.85
Confidence Interval(2-sided) 95%
-1.35 to -0.34
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 22
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 12 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0582
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.50
Confidence Interval(2-sided) 95%
-1.01 to 0.02
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 23
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 12 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0089
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.76
Confidence Interval(2-sided) 95%
-1.32 to -0.19
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 24
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 13 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.9575
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.02
Confidence Interval(2-sided) 95%
-0.57 to 0.61
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 25
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 13 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.2745
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.36
Confidence Interval(2-sided) 95%
-1.01 to 0.29
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 26
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 14 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.7088
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.13
Confidence Interval(2-sided) 95%
-0.81 to 0.55
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 27
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 14 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.3077
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.39
Confidence Interval(2-sided) 95%
-1.13 to 0.36
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 28
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 15 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.7112
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.15
Confidence Interval(2-sided) 95%
-0.93 to 0.63
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 29
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 15 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0837
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.79
Confidence Interval(2-sided) 95%
-1.69 to 0.11
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 30
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 16 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.8655
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.08
Confidence Interval(2-sided) 95%
-0.88 to 1.04
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 31
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 16 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.9725
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.02
Confidence Interval(2-sided) 95%
-1.07 to 1.11
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 32
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 17 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.5285
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.38
Confidence Interval(2-sided) 95%
-0.80 to 1.55
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 33
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 17 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.9663
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.03
Confidence Interval(2-sided) 95%
-1.34 to 1.40
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 34
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 18 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.9914
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.01
Confidence Interval(2-sided) 95%
-1.61 to 1.63
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 35
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 18 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.8345
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.22
Confidence Interval(2-sided) 95%
-1.85 to 2.30
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 36
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 19 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.7725
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.50
Confidence Interval(2-sided) 95%
-2.90 to 3.91
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
26. Secondary Outcome:
Title Change From Baseline in Symptom Severity as Determined by MDASI Part I Score
Description The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part I, participants were asked to rate how severe the symptoms (pain, fatigue, nausea, disturbed sleep, feeling of being distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, feeling sad, vomiting, numbness or tingling, rash/skin changes, headache, mouth/throat sores, and diarrhea) were when "at their worst" in the last 24 hours. Each item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Mixed-effects model-estimated LS mean score for change from baseline at the end-of treatment is reported for each item, where a negative value indicates improvement.
Time Frame Baseline; End of Treatment (EoT) visit (up to approximately 27 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the PRO-Evaluable Population. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed337 358
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Pain: Change at EoT
1.41(0.15) 0.92(0.15)
Fatigue: Change at EoT
1.83(0.15) 1.20(0.15)
Nausea: Change at EoT
1.20(0.11) 0.29(0.11)
Disturbed sleep: Change at EoT
0.71(0.14) 0.19(0.14)
Feelings of being distressed: Change at EoT
0.82(0.14) 0.25(0.14)
Shortness of breath: Change at EoT
1.15(0.13) 0.58(0.13)
Remembering things: Change at EoT
0.93(0.12) 0.60(0.11)
Lack of appetite: Change at EoT
1.59(0.14) 0.40(0.14)
Drowsy: Change at EoT
1.32(0.14) 0.79(0.14)
Dry mouth: Change at EoT
1.67(0.15) 0.67(0.15)
Feeling sad: Change at EoT
0.88(0.14) 0.28(0.14)
Vomiting: Change at EoT
0.66(0.09) 0.08(0.09)
Numbness or tingling: Change at EoT
1.01(0.12) 0.67(0.12)
Rash/skin changes: Change at EoT
2.08(0.13) 1.00(0.13)
Headache: Change at EoT
0.70(0.11) 0.66(0.11)
Mouth/throat sores: Change at EoT
1.76(0.13) 0.74(0.13)
Diarrhea: Change at EoT
1.37(0.10) 0.29(0.10)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsPain: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0010
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.49
Confidence Interval(2-sided) 95%
-0.77 to -0.20
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 2
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsFatigue: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.63
Confidence Interval(2-sided) 95%
-0.91 to -0.34
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 3
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsNausea: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.91
Confidence Interval(2-sided) 95%
-1.13 to -0.69
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 4
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsDisturbed sleep: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0002
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.52
Confidence Interval(2-sided) 95%
-0.79 to -0.25
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 5
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsFeelings of being distressed: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.56
Confidence Interval(2-sided) 95%
-0.84 to -0.29
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 6
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsShortness of breath: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.56
Confidence Interval(2-sided) 95%
-0.81 to -0.32
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 7
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsRemembering things: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0036
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.33
Confidence Interval(2-sided) 95%
-0.56 to -0.11
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 8
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsLack of appetite: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-1.19
Confidence Interval(2-sided) 95%
-1.46 to -0.91
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 9
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsDrowsy: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0001
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.54
Confidence Interval(2-sided) 95%
-0.81 to -0.27
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 10
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsDry mouth: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-1.00
Confidence Interval(2-sided) 95%
-1.28 to -0.71
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 11
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsFeeling sad: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.60
Confidence Interval(2-sided) 95%
-0.87 to -0.33
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 12
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsVomiting: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.58
Confidence Interval(2-sided) 95%
-0.75 to -0.41
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 13
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsNumbness or tingling: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0051
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.34
Confidence Interval(2-sided) 95%
-0.58 to -0.10
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 14
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsRash/Skin Changes: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-1.08
Confidence Interval(2-sided) 95%
-1.33 to -0.83
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 15
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsHeadache: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.6541
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-0.05
Confidence Interval(2-sided) 95%
-0.26 to 0.16
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 16
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsMouth/Throat Sores: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-1.02
Confidence Interval(2-sided) 95%
-1.28 to -0.76
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 17
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsDiarrhea: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodMixed Models Analysis
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value-1.07
Confidence Interval(2-sided) 95%
-1.27 to -0.88
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
27. Secondary Outcome:
Title Change From Baseline in Symptom Severity as Determined by Brief Fatigue Inventory (BFI) Interference Scale Score
Description The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI interference subscale (6 items) assessed the impact of fatigue on global domains (general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely). Change from baseline in the mean score of all 6 items at each timepoint is reported, where a negative value indicates improvement.
Time Frame Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days
Outcome Measure Data
Analysis Population Description
Analysis was performed on the PRO-Evaluable Population. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure; 'Number Analyzed' = number of participants evaluable at specified time point.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed368 381
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline
2.11(2.23) 2.08(2.38)
Change at Cycle 1 Day 8
0.30(1.88) 0.37(1.76)
Change at Cycle 1 Day 15
1.26(2.49) 1.06(2.42)
Change at Cycle 1 Day 22
1.34(2.44) 0.57(2.04)
Change at Cycle 1 Day 29
1.48(2.63) 0.66(2.28)
Change at Cycle 1 Day 36
0.95(2.29) 0.74(2.20)
Change at Cycle 2 Day 1
0.38(2.03) 0.43(2.09)
Change at Cycle 2 Day 8
0.63(2.17) 0.68(2.33)
Change at Cycle 2 Day 15
1.10(2.35) 0.55(2.29)
Change at Cycle 2 Day 22
1.24(2.65) 0.26(2.14)
Change at Cycle 2 Day 29
1.45(2.61) 0.51(2.14)
Change at Cycle 2 Day 36
1.11(2.46) 0.43(2.17)
Change at Cycle 3 Day 1
0.76(2.27) 0.21(2.12)
Change at Cycle 3 Day 22
1.43(2.41) 0.36(2.20)
Change at Cycle 4 Day 1
0.76(2.27) 0.38(2.16)
Change at Cycle 4 Day 22
1.47(2.60) 0.44(2.33)
Change at Cycle 5 Day 1
1.01(2.46) 0.52(2.31)
Change at Cycle 5 Day 22
1.38(2.22) 0.61(2.27)
Change at Cycle 6 Day 1
0.88(2.24) 0.59(2.15)
Change at Cycle 6 Day 22
1.25(2.42) 0.52(2.22)
Change at Cycle 7 Day 1
0.82(2.35) 0.61(2.17)
Change at Cycle 7 Day 22
1.05(2.31) 0.47(2.16)
Change at Cycle 8 Day 1
0.87(2.21) 0.63(2.36)
Change at Cycle 8 Day 22
1.22(2.21) 0.52(2.05)
Change at Cycle 9 Day 1
0.93(2.25) 0.57(2.27)
Change at Cycle 9 Day 22
1.35(2.37) 0.37(2.15)
Change at Cycle 10 Day 1
1.09(2.53) 0.56(1.96)
Change at Cycle 10 Day 22
1.62(2.75) 0.52(1.95)
Change at Cycle 11 Day 1
0.95(2.29) 0.60(1.92)
Change at Cycle 11 Day 22
0.88(2.57) 0.57(1.78)
Change at Cycle 12 Day 1
0.89(2.45) 0.35(1.75)
Change at Cycle 12 Day 22
0.97(2.46) 0.58(1.96)
Change at Cycle 13 Day 1
0.84(2.29) 0.36(1.88)
Change at Cycle 13 Day 22
0.76(2.70) 0.56(2.06)
Change at Cycle 14 Day 1
0.80(2.33) 0.73(1.80)
Change at Cycle 14 Day 22
0.69(2.73) 0.94(1.96)
Change at Cycle 15 Day 1
0.95(2.42) 0.61(1.41)
Change at Cycle 15 Day 22
1.05(3.22) 0.91(1.28)
Change at Cycle 16 Day 1
0.13(1.49) 1.02(1.69)
Change at Cycle 16 Day 22
1.05(1.83) 1.55(1.96)
Change at Cycle 17 Day 1
0.53(1.41) 1.25(1.97)
Change at Cycle 17 Day 22
1.43(2.16) 0.41(1.48)
Change at Cycle 18 Day 1
0.79(1.34) 0.35(1.46)
Change at Cycle 18 Day 22
1.28(2.21) 0.17(1.15)
Change at Cycle 19 Day 1
0.00() -0.80(0.84)
Change at Cycle 19 Day 22
 -0.25(0.82)
Change at 6 weeks after EoT
2.31(2.52) 1.83(2.52)
Change at 12 weeks after EoT
1.71(2.66) 1.97(2.63)
Change at 24 weeks after EoT
2.38(3.11) 2.15(3.30)
Change at 36 weeks after EoT
2.40(3.32) 1.15(2.72)
Change at EoT
1.57(2.80) 1.62(2.98)
Change Within 30 Days of PD
1.74(2.64) 0.74(2.35)
28. Secondary Outcome:
Title Change From Baseline in Symptom Severity as Determined by BFI Worst Fatigue Item
Description The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI worst fatigue item assessed the severity of fatigue at its worst in the last 24 hours. The item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Change from baseline in the score at each time point is reported, where a negative value indicates improvement.
Time Frame Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days
Outcome Measure Data
Analysis Population Description
Analysis was performed on the PRO-Evaluable Population. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure; 'Number Analyzed' = number of participants evaluable at specified time point.
 
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed368 381
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline
3.08(2.66) 2.98(2.69)
Change at Cycle 1 Day 8
0.34(2.35) 0.50(2.29)
Change at Cycle 1 Day 15
1.32(2.82) 1.26(2.92)
Change at Cycle 1 Day 22
1.52(2.86) 0.49(2.30)
Change at Cycle 1 Day 29
1.55(2.99) 0.88(2.62)
Change at Cycle 1 Day 36
0.77(2.82) 0.86(2.50)
Change at Cycle 2 Day 1
0.40(2.50) 0.45(2.52)
Change at Cycle 2 Day 8
0.56(2.68) 0.87(2.82)
Change at Cycle 2 Day 15
1.09(2.82) 0.71(2.78)
Change at Cycle 2 Day 22
1.42(3.01) 0.31(2.53)
Change at Cycle 2 Day 29
1.43(3.08) 0.62(2.66)
Change at Cycle 2 Day 36
1.09(3.01) 0.48(2.76)
Change at Cycle 3 Day 1
0.42(2.68) 0.40(2.57)
Change at Cycle 3 Day 22
1.57(2.98) 0.57(2.64)
Change at Cycle 4 Day 1
0.64(2.76) 0.54(2.49)
Change at Cycle 4 Day 22
1.46(3.14) 0.58(2.74)
Change at Cycle 5 Day 1
0.81(2.75) 0.62(2.79)
Change at Cycle 5 Day 22
1.60(2.87) 0.69(2.83)
Change at Cycle 6 Day 1
0.90(2.78) 0.86(2.73)
Change at Cycle 6 Day 22
1.35(2.79) 0.53(2.66)
Change at Cycle 7 Day 1
0.79(2.78) 0.79(2.70)
Change at Cycle 7 Day 22
1.22(2.85) 0.65(2.56)
Change at Cycle 8 Day 1
0.79(2.69) 0.75(2.84)
Change at Cycle 8 Day 22
1.40(2.64) 0.78(2.67)
Change at Cycle 9 Day 1
0.97(2.54) 0.61(2.62)
Change at Cycle 9 Day 22
1.54(2.92) 0.57(2.55)
Change at Cycle 10 Day 1
0.95(2.73) 0.69(2.46)
Change at Cycle 10 Day 22
1.74(3.09) 0.63(2.48)
Change at Cycle 11 Day 1
0.73(2.80) 0.74(2.69)
Change at Cycle 11 Day 22
1.15(3.18) 0.74(2.52)
Change at Cycle 12 Day 1
0.78(2.79) 0.61(2.29)
Change at Cycle 12 Day 22
1.32(2.89) 0.74(2.69)
Change at Cycle 13 Day 1
0.35(2.54) 0.49(2.46)
Change at Cycle 13 Day 22
0.72(3.48) 0.65(2.70)
Change at Cycle 14 Day 1
0.56(2.84) 0.81(2.60)
Change at Cycle 14 Day 22
0.37(3.01) 1.04(2.40)
Change at Cycle 15 Day 1
0.52(3.15) 0.93(2.25)
Change at Cycle 15 Day 22
0.59(4.08) 0.97(1.84)
Change at Cycle 16 Day 1
-0.05(2.61) 1.33(1.92)
Change at Cycle 16 Day 22
0.77(3.70) 1.68(2.10)
Change at Cycle 17 Day 1
-0.62(3.75) 1.68(1.97)
Change at Cycle 17 Day 22
1.44(3.91) 1.18(1.99)
Change at Cycle 18 Day 1
0.00(2.00) 1.33(1.58)
Change at Cycle 18 Day 22
1.00(1.73) 1.00(2.10)
Change at Cycle 19 Day 1
-4.00() 0.60(1.34)
Change at Cycle 19 Day 22
 0.00(0.00)
Change at 6 weeks after EoT
2.43(3.25) 2.40(2.89)
Change at 12 weeks after EoT
1.56(3.41) 2.06(3.14)
Change at 24 weeks after EoT
1.58(3.82) 1.92(3.46)
Change at 36 weeks after EoT
1.86(4.37) 0.78(2.86)
Change at EoT
1.40(3.13) 1.72(2.84)
Change Within 30 Days of PD
1.81(3.16) 0.89(2.58)
29. Secondary Outcome:
Title Change From Baseline in Treatment Side Effects Burden as Determined by Functional Assessment of Cancer Therapy Kidney Symptom Index (FKSI-19) General Population 5 (GP5) Item Score
Description The FKSI-19 is a 19-item tool designed to assess the most important symptoms and concerns related to treatment effectiveness in advanced kidney cancer. The FKSI-19 GP5 item (bothered by the side effect of treatment) assessed side effects burden in the past 7 days on a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Repeated measures model-estimated LS mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement.
Time Frame Day 1 and 22 of every cycle (Baseline = Day 1 Cycle 1) up to Cycle 19; Cycle length = 42 days
Outcome Measure Data
Analysis Population Description
Analysis was performed on the PRO-Evaluable Population. Here, 'Number Analyzed' = number of participants evaluable at specified time point.
   
Arm/Group TitleSunitinibAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed359 373
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
 
Change at Cycle1 Day 22
Number Analyzed Participants Participants
-1.08(0.06) -0.36(0.06)
Change at Cycle 2 Day 1
Number Analyzed Participants Participants
-0.87(0.06) -0.45(0.06)
Change at Cycle 2 Day 22
Number Analyzed Participants Participants
-1.13(0.06) -0.43(0.06)
Change at Cycle 3 Day 1
Number Analyzed Participants Participants
-1.07(0.06) -0.49(0.06)
Change at Cycle 3 Day 22
Number Analyzed Participants Participants
-1.22(0.06) -0.45(0.06)
Change at Cycle 4 Day 1
Number Analyzed Participants Participants
-1.07(0.06) -0.45(0.06)
Change at Cycle 4 Day 22
Number Analyzed Participants Participants
-1.31(0.07) -0.49(0.06)
Change at Cycle 5 Day 1
Number Analyzed Participants Participants
-1.17(0.07) -0.52(0.06)
Change at Cycle 5 Day 22
Number Analyzed Participants Participants
-1.38(0.07) -0.55(0.06)
Change at Cycle 6 Day 1
Number Analyzed Participants Participants
-1.14(0.07) -0.51(0.06)
Change at Cycle 6 Day 22
Number Analyzed Participants Participants
-1.27(0.07) -0.56(0.07)
Change at Cycle 7 Day 1
Number Analyzed Participants Participants
-1.09(0.07) -0.61(0.07)
Change at Cycle 7 Day 22
Number Analyzed Participants Participants
-1.25(0.07) -0.58(0.07)
Change at Cycle 8 Day 1
Number Analyzed Participants Participants
-1.08(0.08) -0.61(0.07)
Change at Cycle 8 Day 22
Number Analyzed Participants Participants
-1.22(0.08) -0.62(0.07)
Change at Cycle 9 Day 1
Number Analyzed Participants Participants
-1.08(0.08) -0.60(0.07)
Change at Cycle 9 Day 22
Number Analyzed Participants Participants
-1.23(0.08) -0.52(0.07)
Change at Cycle 10 Day 1
Number Analyzed Participants Participants
-1.06(0.08) -0.53(0.07)
Change at Cycle 10 Day 22
Number Analyzed Participants Participants
-1.30(0.09) -0.57(0.08)
Change at Cycle 11 Day 1
Number Analyzed Participants Participants
-1.16(0.09) -0.52(0.08)
Change at Cycle 11 Day 22
Number Analyzed Participants Participants
-1.28(0.11) -0.54(0.08)
Change at Cycle 12 Day 1
Number Analyzed Participants Participants
-1.05(0.10) -0.62(0.09)
Change at Cycle 12 Day 22
Number Analyzed Participants Participants
-1.17(0.12) -0.56(0.09)
Change at Cycle 13 Day 1
Number Analyzed Participants Participants
-1.15(0.12) -0.62(0.10)
Change at Cycle 13 Day 22
Number Analyzed Participants Participants
-1.20(0.14) -0.64(0.11)
Change at Cycle 14 Day 1
Number Analyzed Participants Participants
-0.94(0.14) -0.61(0.12)
Change at Cycle 14 Day 22
Number Analyzed Participants Participants
-1.32(0.16) -0.65(0.12)
Change at Cycle 15 Day 1
Number Analyzed Participants Participants
-0.91(0.15) -0.62(0.13)
Change at Cycle 15 Day 22
Number Analyzed Participants Participants
-1.16(0.19) -0.72(0.14)
Change at Cycle 16 Day 1
Number Analyzed Participants Participants
-1.06(0.19) -0.58(0.16)
Change at Cycle 16 Day 22
Number Analyzed Participants Participants
-1.34(0.22) -0.41(0.18)
Change at Cycle 17 Day 1
Number Analyzed Participants Participants
-1.10(0.23) -0.56(0.20)
Change at Cycle 17 Day 22
Number Analyzed Participants Participants
-1.02(0.27) -0.44(0.24)
Change at Cycle 18 Day 1
Number Analyzed Participants Participants
-1.01(0.33) -0.38(0.27)
Change at Cycle 18 Day 22
Number Analyzed Participants Participants
-0.81(0.46) -0.48(0.33)
Change at Cycle 19 Day 1
Number Analyzed Participants Participants
-1.27(0.84) -0.75(0.38)
Change at Cycle 19 Day 22
Number Analyzed Participants Participants
-0.93(0.55)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 1 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.73
Confidence Interval(2-sided) 95%
0.58 to 0.87
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 2
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 2 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.42
Confidence Interval(2-sided) 95%
0.28 to 0.57
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 3
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 2 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.70
Confidence Interval(2-sided) 95%
0.55 to 0.84
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 4
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 3 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.58
Confidence Interval(2-sided) 95%
0.44 to 0.73
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 5
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 3 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.77
Confidence Interval(2-sided) 95%
0.62 to 0.92
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 6
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 4 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.62
Confidence Interval(2-sided) 95%
0.46 to 0.78
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 7
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 4 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.82
Confidence Interval(2-sided) 95%
0.66 to 0.97
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 8
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 5 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.65
Confidence Interval(2-sided) 95%
0.49 to 0.81
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 9
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 5 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.83
Confidence Interval(2-sided) 95%
0.66 to 0.99
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 10
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 6 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.63
Confidence Interval(2-sided) 95%
0.46 to 0.80
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 11
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 6 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.72
Confidence Interval(2-sided) 95%
0.54 to 0.89
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 12
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 7 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.47
Confidence Interval(2-sided) 95%
0.30 to 0.65
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 13
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 7 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.68
Confidence Interval(2-sided) 95%
0.49 to 0.86
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 14
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 8 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.47
Confidence Interval(2-sided) 95%
0.29 to 0.66
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 15
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 8 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.60
Confidence Interval(2-sided) 95%
0.41 to 0.79
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 16
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 9 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.49
Confidence Interval(2-sided) 95%
0.29 to 0.68
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 17
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 9 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.71
Confidence Interval(2-sided) 95%
0.52 to 0.91
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 18
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 10 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.53
Confidence Interval(2-sided) 95%
0.33 to 0.73
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 19
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 10 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.74
Confidence Interval(2-sided) 95%
0.51 to 0.96
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 20
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 11 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.64
Confidence Interval(2-sided) 95%
0.41 to 0.86
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 21
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 11 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.74
Confidence Interval(2-sided) 95%
0.49 to 0.99
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 22
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 12 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0010
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.42
Confidence Interval(2-sided) 95%
0.17 to 0.68
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 23
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 12 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.60
Confidence Interval(2-sided) 95%
0.32 to 0.89
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 24
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 13 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0005
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.52
Confidence Interval(2-sided) 95%
0.23 to 0.82
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 25
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 13 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0008
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.56
Confidence Interval(2-sided) 95%
0.23 to 0.88
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 26
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 14 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0591
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.33
Confidence Interval(2-sided) 95%
-0.01 to 0.67
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 27
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 14 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0005
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.67
Confidence Interval(2-sided) 95%
0.29 to 1.05
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 28
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 15 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.1378
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.30
Confidence Interval(2-sided) 95%
-0.09 to 0.68
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 29
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 15 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0650
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.43
Confidence Interval(2-sided) 95%
-0.03 to 0.89
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 30
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 16 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0531
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.48
Confidence Interval(2-sided) 95%
-0.01 to 0.96
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 31
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 16 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0011
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.93
Confidence Interval(2-sided) 95%
0.37 to 1.49
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 32
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 17 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0708
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.55
Confidence Interval(2-sided) 95%
-0.05 to 1.14
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 33
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 17 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.1078
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.58
Confidence Interval(2-sided) 95%
-0.13 to 1.29
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 34
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 18 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.1487
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.62
Confidence Interval(2-sided) 95%
-0.22 to 1.47
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 35
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 18 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.5537
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.33
Confidence Interval(2-sided) 95%
-0.77 to 1.43
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Statistical Analysis 36
Statistical Analysis OverviewComparison Group SelectionSunitinib, Atezolizumab + Bevacizumab
CommentsCycle 19 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.5743
Comments[Not specified]
MethodRepeated measures model
Comments[Not specified]
Method of EstimationEstimation ParameterLS Mean Difference
Estimated Value0.52
Confidence Interval(2-sided) 95%
-1.29 to 2.33
Estimation CommentsDifference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
30. Secondary Outcome:
Title Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab
Description The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against atezolizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result. Here, 'Overall Number of Participants Analyzed' = number of participants with a non-missing baseline ATA sample; 'Number Analyzed' = number of participants with a non-missing ATA sample at indicated timepoint.
Time Frame Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycles 2, 4, and 8, and every eight cycles thereafter up to EoT [up to approximately 27 months] and 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ATA-Evaluable Population, which included all participants in the Atezolizumab + Bevacizumab arm with a non-missing baseline ATA sample and >/=1 post-baseline ATA sample.
 
Arm/Group TitleAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed446
Measure Type: Number
Unit of Measure: participants
Baseline: ATA Positive Participants
16
3.6%
Post-Baseline: Treatment-Induced ATA
95
21.3%
Post-Baseline: Treatment-Enhanced ATA
1
0.2%
31. Secondary Outcome:
Title Number of Participants With ATAs Against Bevacizumab
Description The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against bevacizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result.
Time Frame Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycle 3, at EoT [up to approximately 27 months] and at 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the ATA-Evaluable Population. Here, 'Overall Number of Participants Analyzed' = number of participants with a non-missing baseline ATA sample; 'Number Analyzed' = number of participants with a non-missing ATA sample at indicated timepoint.
 
Arm/Group TitleAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed444
Measure Type: Number
Unit of Measure: participants
Baseline: ATA Positive Participants
24
5.4%
Post-Baseline: Treatment-Induced ATA
4
0.9%
Post-Baseline: Treatment-Enhanced ATA
0
0%
32. Secondary Outcome:
Title Maximum Observed Serum Concentration (Cmax) for Atezolizumab
Description Cmax for atezolizumab was estimated from plasma concentration versus time data.
Time Frame 30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the Atezolizumab Pharmacokinetic (PK) Population, which included all participants who received atezolizumab treatment and had evaluable PK samples. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure.
 
Arm/Group TitleAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed435
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter (mcg/mL)
376(90.2)
33. Secondary Outcome:
Title Minimum Observed Serum Concentration (Cmin) for Atezolizumab
Description Cmin for atezolizumab was estimated from plasma concentration versus time data.
Time Frame Predose (Hour 0) on Day 22 of Cycle 1; predose (Hour 0) on Day 1 of Cycles 2; Cycle length = 42 days
Outcome Measure Data
Analysis Population Description
Analysis was performed on the Atezolizumab PK Population. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure; 'Number Analyzed' = number of participants evaluable at specified time point.
 
Arm/Group TitleAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed426
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Cycle 1 Day 22
85.6(35.3)
Cycle 2 Day 1
127(49.6)
34. Secondary Outcome:
Title Cmax for Bevacizumab
Description Cmax for bevacizumab was estimated from plasma concentration versus time data.
Time Frame 30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the Bevacizumab PK Population, which included all participants who received bevacizumab treatment and had evaluable PK samples. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure.
 
Arm/Group TitleAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed427
Mean (Standard Deviation)
Unit of Measure: mcg/mL
339(104)
35. Secondary Outcome:
Title Cmin for Bevacizumab
Description Cmin for bevacizumab was estimated from plasma concentration versus time data.
Time Frame Pre-dose (Hour 0) on Day 1 of Cycle 3 (Cycle length = 42 days)
Outcome Measure Data
Analysis Population Description
Analysis was performed on the Bevacizumab PK Population. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure.
 
Arm/Group TitleAtezolizumab + Bevacizumab
Arm/Group DescriptionParticipants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed363
Mean (Standard Deviation)
Unit of Measure: mcg/mL
135(56.1)
Open or close this module Adverse Events
 
Time Frame Baseline up to data cut-off date 29 September 2017(overall approximately 27 months)
Adverse Event Reporting Description Analysis was performed on the safety-evaluable (SE) population, which included all randomized participants who received any amount of any component of the study treatments.
 
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Arm/Group Description Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first. Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
All-Cause Mortality
  SunitinibAtezolizumab + Bevacizumab
 Affected / At Risk (%)Affected / At Risk (%)
Total 135 / 446 (30.27%)122 / 451 (27.05%)
Serious Adverse Events
  SunitinibAtezolizumab + Bevacizumab
 Affected / At Risk (%)Affected / At Risk (%)
Total 149 / 446 (33.41%)174 / 451 (38.58%)
Blood and lymphatic system disorders
Anaemia ∗ A 3 / 446 (0.67%)3 / 451 (0.67%)
Factor VIII inhibition ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Febrile neutropenia ∗ A 2 / 446 (0.45%)0 / 451 (0%)
Thrombocytopenia ∗ A 4 / 446 (0.9%)0 / 451 (0%)
Cardiac disorders
Acute coronary syndrome ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Angina pectoris ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Atrial fibrillation ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Atrioventricular block complete ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Cardiac arrest ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Cardiac failure ∗ A 0 / 446 (0%)3 / 451 (0.67%)
Myocardial infarction ∗ A 0 / 446 (0%)3 / 451 (0.67%)
Myocarditis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Ear and labyrinth disorders
Vertigo ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Endocrine disorders
Adrenal insufficiency ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Hypothyroidism ∗ A 6 / 446 (1.35%)1 / 451 (0.22%)
Gastrointestinal disorders
Abdominal pain ∗ A 2 / 446 (0.45%)4 / 451 (0.89%)
Abdominal pain upper ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Anal fistula ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Ascites ∗ A 2 / 446 (0.45%)0 / 451 (0%)
Autoimmune colitis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Colitis ∗ A 1 / 446 (0.22%)4 / 451 (0.89%)
Constipation ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Diarrhoea ∗ A 2 / 446 (0.45%)7 / 451 (1.55%)
Duodenal obstruction ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Duodenal ulcer ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Enteritis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Gastric haemorrhage ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Gastrointestinal fistula ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Gastrointestinal haemorrhage ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Ileus ∗ A 1 / 446 (0.22%)2 / 451 (0.44%)
Intestinal perforation ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Large intestine perforation ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Lower gastrointestinal haemorrhage ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Nausea ∗ A 3 / 446 (0.67%)1 / 451 (0.22%)
Oesophageal perforation ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Pancreatitis ∗ A 2 / 446 (0.45%)1 / 451 (0.22%)
Small intestinal haemorrhage ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Small intestinal perforation ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Stomatitis ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Upper gastrointestinal haemorrhage ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Vomiting ∗ A 5 / 446 (1.12%)3 / 451 (0.67%)
General disorders
Asthenia ∗ A 3 / 446 (0.67%)3 / 451 (0.67%)
Chest pain ∗ A 4 / 446 (0.9%)1 / 451 (0.22%)
Chills ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Death ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Fatigue ∗ A 2 / 446 (0.45%)1 / 451 (0.22%)
General physical health deterioration ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Ill-defined disorder ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Influenza like illness ∗ A 1 / 446 (0.22%)3 / 451 (0.67%)
Infusion site extravasation ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Malaise ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Mucosal inflammation ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Multiple organ dysfunction syndrome ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Non-cardiac chest pain ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Oedema ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Oedema peripheral ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Pain ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Performance status decreased ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Pyrexia ∗ A 7 / 446 (1.57%)12 / 451 (2.66%)
Systemic inflammatory response syndrome ∗ A 0 / 446 (0%)3 / 451 (0.67%)
Hepatobiliary disorders
Autoimmune hepatitis ∗ A 0 / 446 (0%)4 / 451 (0.89%)
Biliary colic ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Cholecystitis ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Cholelithiasis ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Drug-induced liver injury ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Hepatic function abnormal ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Hepatic steatosis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Hepatitis ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Hepatotoxicity ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Jaundice ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Immune system disorders
Cytokine release syndrome ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Drug hypersensitivity ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Hypersensitivity ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Systemic immune activation ∗ A 0 / 446 (0%)3 / 451 (0.67%)
Infections and infestations
Abscess ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Appendicitis ∗ A 2 / 446 (0.45%)0 / 451 (0%)
Appendicitis perforated ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Cellulitis ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Clostridium difficile infection ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Cystitis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Device related infection ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Diverticulitis ∗ A 1 / 446 (0.22%)2 / 451 (0.44%)
Empyema ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Encephalitis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Febrile infection ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Gastroenteritis ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Haematoma infection ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Herpes zoster ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Infection ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Influenza ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Lower respiratory tract infection ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Lung abscess ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Lung infection ∗ A 1 / 446 (0.22%)2 / 451 (0.44%)
Meningitis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Meningitis aseptic ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Orchitis ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Osteomyelitis ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Perirectal abscess ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Peritonitis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Pilonidal cyst ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Pneumonia ∗ A 4 / 446 (0.9%)7 / 451 (1.55%)
Pneumonia viral ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Pyelonephritis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Respiratory tract infection ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Scrotal abscess ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Sepsis ∗ A 2 / 446 (0.45%)3 / 451 (0.67%)
Septic shock ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Staphylococcal bacteraemia ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Subcutaneous abscess ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Upper respiratory tract infection ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Urinary tract infection ∗ A 1 / 446 (0.22%)2 / 451 (0.44%)
Urosepsis ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Wound infection ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Injury, poisoning and procedural complications
Conjunctival laceration ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Fall ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Femoral neck fracture ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Femur fracture ∗ A 2 / 446 (0.45%)1 / 451 (0.22%)
Gastrointestinal anastomotic leak ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Infusion related reaction ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Injury ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Post procedural haemorrhage ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Road traffic accident ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Seroma ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Tooth injury ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Upper limb fracture ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Wound complication ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Investigations
Blood creatine phosphokinase increased ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Blood creatinine increased ∗ A 1 / 446 (0.22%)2 / 451 (0.44%)
Blood sodium decreased ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Hepatic enzyme increased ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Lipase increased ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Liver function test increased ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Platelet count decreased ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Troponin increased ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Weight decreased ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Metabolism and nutrition disorders
Cachexia ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Decreased appetite ∗ A 2 / 446 (0.45%)1 / 451 (0.22%)
Dehydration ∗ A 7 / 446 (1.57%)3 / 451 (0.67%)
Diabetes mellitus ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Diabetes mellitus inadequate control ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Hypercalcaemia ∗ A 5 / 446 (1.12%)3 / 451 (0.67%)
Hyperglycaemia ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Hyperkalaemia ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Hypoglycaemia ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Hyponatraemia ∗ A 3 / 446 (0.67%)4 / 451 (0.89%)
Hypophosphataemia ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Musculoskeletal and connective tissue disorders
Arthralgia ∗ A 1 / 446 (0.22%)3 / 451 (0.67%)
Back pain ∗ A 3 / 446 (0.67%)1 / 451 (0.22%)
Bone pain ∗ A 1 / 446 (0.22%)2 / 451 (0.44%)
Bursitis ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Fistula ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Flank pain ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Groin pain ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Intervertebral disc protrusion ∗ A 2 / 446 (0.45%)0 / 451 (0%)
Joint swelling ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Mobility decreased ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Muscle haemorrhage ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Muscular weakness ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Musculoskeletal chest pain ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Myalgia ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Myositis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Pain in extremity ∗ A 1 / 446 (0.22%)4 / 451 (0.89%)
Rhabdomyolysis ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholangiocarcinoma ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Colon neoplasm ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Gastric cancer stage III ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Intracranial tumour haemorrhage ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Prostate cancer ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Tumour haemorrhage ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Nervous system disorders
Altered state of consciousness ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Aphasia ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Cerebral infarction ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Cerebral ischaemia ∗ A 2 / 446 (0.45%)0 / 451 (0%)
Cerebrovascular accident ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Coma ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Depressed level of consciousness ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Dizziness ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Gliosis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Haemorrhage intracranial ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Haemorrhagic stroke ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Headache ∗ A 2 / 446 (0.45%)0 / 451 (0%)
Intracranial pressure increased ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Ischaemic stroke ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Lacunar infarction ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Lethargy ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Lumbosacral plexopathy ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Neuropathy peripheral ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Paraplegia ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Peripheral sensory neuropathy ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Seizure ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Spinal cord compression ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Syncope ∗ A 2 / 446 (0.45%)2 / 451 (0.44%)
Thalamus haemorrhage ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Transient ischaemic attack ∗ A 1 / 446 (0.22%)2 / 451 (0.44%)
Psychiatric disorders
Mental status changes ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Psychotic disorder ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Renal and urinary disorders
Acute kidney injury ∗ A 10 / 446 (2.24%)9 / 451 (2%)
Chronic kidney disease ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Haematuria ∗ A 3 / 446 (0.67%)1 / 451 (0.22%)
Nephritis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Nephrolithiasis ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Nephrotic syndrome ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Proteinuria ∗ A 0 / 446 (0%)3 / 451 (0.67%)
Renal failure ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Renal impairment ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Tubulointerstitial nephritis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Ureteric obstruction ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Urinary retention ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Reproductive system and breast disorders
Prostatitis ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Atelectasis ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Dyspnoea ∗ A 5 / 446 (1.12%)4 / 451 (0.89%)
Epistaxis ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Hypoxia ∗ A 1 / 446 (0.22%)1 / 451 (0.22%)
Interstitial lung disease ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Laryngeal oedema ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Pleural effusion ∗ A 1 / 446 (0.22%)3 / 451 (0.67%)
Pleurisy ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Pneumonia aspiration ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Pneumonitis ∗ A 0 / 446 (0%)7 / 451 (1.55%)
Pneumothorax ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Pulmonary embolism ∗ A 5 / 446 (1.12%)4 / 451 (0.89%)
Pulmonary infarction ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Pulmonary pain ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Skin and subcutaneous tissue disorders
Rash macular ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Rash maculo-papular ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Toxic epidermal necrolysis ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Surgical and medical procedures
Fracture treatment ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Hernia repair ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Tooth extraction ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Vascular disorders
Aortic disorder ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Aortic dissection ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Embolism ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Haematoma ∗ A 0 / 446 (0%)2 / 451 (0.44%)
Hypertension ∗ A 1 / 446 (0.22%)2 / 451 (0.44%)
Hypotension ∗ A 1 / 446 (0.22%)2 / 451 (0.44%)
Peripheral artery aneurysm ∗ A 1 / 446 (0.22%)0 / 451 (0%)
Peripheral ischaemia ∗ A 0 / 446 (0%)1 / 451 (0.22%)
Shock haemorrhagic ∗ A 1 / 446 (0.22%)0 / 451 (0%)
∗Indicates events were collected by non-systematic methods.
ATerm from vocabulary, MedDRA Version 20.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
  SunitinibAtezolizumab + Bevacizumab
 Affected / At Risk (%)Affected / At Risk (%)
Total 433 / 446 (97.09%)434 / 451 (96.23%)
Blood and lymphatic system disorders
Anaemia ∗ A 91 / 446 (20.4%)40 / 451 (8.87%)
Leukopenia ∗ A 26 / 446 (5.83%)5 / 451 (1.11%)
Neutropenia ∗ A 55 / 446 (12.33%)3 / 451 (0.67%)
Thrombocytopenia ∗ A 78 / 446 (17.49%)13 / 451 (2.88%)
Endocrine disorders
Hyperthyroidism ∗ A 14 / 446 (3.14%)32 / 451 (7.1%)
Hypothyroidism ∗ A 111 / 446 (24.89%)99 / 451 (21.95%)
Gastrointestinal disorders
Abdominal pain ∗ A 38 / 446 (8.52%)40 / 451 (8.87%)
Abdominal pain upper ∗ A 36 / 446 (8.07%)16 / 451 (3.55%)
Constipation ∗ A 62 / 446 (13.9%)79 / 451 (17.52%)
Diarrhoea ∗ A 230 / 446 (51.57%)128 / 451 (28.38%)
Dry mouth ∗ A 25 / 446 (5.61%)31 / 451 (6.87%)
Dyspepsia ∗ A 84 / 446 (18.83%)28 / 451 (6.21%)
Gastrooesophageal reflux disease ∗ A 51 / 446 (11.43%)9 / 451 (2%)
Nausea ∗ A 167 / 446 (37.44%)87 / 451 (19.29%)
Stomatitis ∗ A 99 / 446 (22.2%)45 / 451 (9.98%)
Toothache ∗ A 14 / 446 (3.14%)25 / 451 (5.54%)
Vomiting ∗ A 111 / 446 (24.89%)54 / 451 (11.97%)
General disorders
Asthenia ∗ A 103 / 446 (23.09%)79 / 451 (17.52%)
Chest pain ∗ A 24 / 446 (5.38%)15 / 451 (3.33%)
Fatigue ∗ A 166 / 446 (37.22%)150 / 451 (33.26%)
Influenza like illness ∗ A 19 / 446 (4.26%)38 / 451 (8.43%)
Mucosal inflammation ∗ A 125 / 446 (28.03%)41 / 451 (9.09%)
Oedema peripheral ∗ A 45 / 446 (10.09%)51 / 451 (11.31%)
Pain ∗ A 12 / 446 (2.69%)24 / 451 (5.32%)
Pyrexia ∗ A 50 / 446 (11.21%)69 / 451 (15.3%)
Infections and infestations
Nasopharyngitis ∗ A 32 / 446 (7.17%)36 / 451 (7.98%)
Upper respiratory tract infection ∗ A 25 / 446 (5.61%)33 / 451 (7.32%)
Urinary tract infection ∗ A 15 / 446 (3.36%)24 / 451 (5.32%)
Investigations
Alanine aminotransferase increased ∗ A 34 / 446 (7.62%)26 / 451 (5.76%)
Aspartate aminotransferase increased ∗ A 35 / 446 (7.85%)25 / 451 (5.54%)
Blood creatinine increased ∗ A 36 / 446 (8.07%)35 / 451 (7.76%)
Neutrophil count decreased ∗ A 24 / 446 (5.38%)3 / 451 (0.67%)
Platelet count decreased ∗ A 46 / 446 (10.31%)1 / 451 (0.22%)
Weight decreased ∗ A 25 / 446 (5.61%)34 / 451 (7.54%)
Metabolism and nutrition disorders
Decreased appetite ∗ A 142 / 446 (31.84%)83 / 451 (18.4%)
Hyperkalaemia ∗ A 13 / 446 (2.91%)28 / 451 (6.21%)
Hyponatraemia ∗ A 16 / 446 (3.59%)25 / 451 (5.54%)
Musculoskeletal and connective tissue disorders
Arthralgia ∗ A 56 / 446 (12.56%)102 / 451 (22.62%)
Back pain ∗ A 55 / 446 (12.33%)72 / 451 (15.96%)
Musculoskeletal pain ∗ A 23 / 446 (5.16%)40 / 451 (8.87%)
Myalgia ∗ A 21 / 446 (4.71%)57 / 451 (12.64%)
Pain in extremity ∗ A 33 / 446 (7.4%)41 / 451 (9.09%)
Nervous system disorders
Dizziness ∗ A 24 / 446 (5.38%)50 / 451 (11.09%)
Dysgeusia ∗ A 128 / 446 (28.7%)31 / 451 (6.87%)
Headache ∗ A 76 / 446 (17.04%)99 / 451 (21.95%)
Psychiatric disorders
Anxiety ∗ A 15 / 446 (3.36%)30 / 451 (6.65%)
Insomnia ∗ A 35 / 446 (7.85%)35 / 451 (7.76%)
Renal and urinary disorders
Haematuria ∗ A 23 / 446 (5.16%)12 / 451 (2.66%)
Proteinuria ∗ A 29 / 446 (6.5%)91 / 451 (20.18%)
Respiratory, thoracic and mediastinal disorders
Cough ∗ A 87 / 446 (19.51%)96 / 451 (21.29%)
Dysphonia ∗ A 18 / 446 (4.04%)61 / 451 (13.53%)
Dyspnoea ∗ A 43 / 446 (9.64%)56 / 451 (12.42%)
Epistaxis ∗ A 65 / 446 (14.57%)73 / 451 (16.19%)
Oropharyngeal pain ∗ A 16 / 446 (3.59%)37 / 451 (8.2%)
Rhinorrhoea ∗ A 9 / 446 (2.02%)30 / 451 (6.65%)
Skin and subcutaneous tissue disorders
Dry skin ∗ A 37 / 446 (8.3%)40 / 451 (8.87%)
Hair colour changes ∗ A 31 / 446 (6.95%)0 / 451 (0%)
Palmar-plantar erythrodysaesthesia syndrome ∗ A 195 / 446 (43.72%)20 / 451 (4.43%)
Pruritus ∗ A 30 / 446 (6.73%)95 / 451 (21.06%)
Rash ∗ A 66 / 446 (14.8%)85 / 451 (18.85%)
Skin discolouration ∗ A 28 / 446 (6.28%)0 / 451 (0%)
Yellow skin ∗ A 28 / 446 (6.28%)1 / 451 (0.22%)
Vascular disorders
Hypertension ∗ A 189 / 446 (42.38%)168 / 451 (37.25%)
∗Indicates events were collected by non-systematic methods.
ATerm from vocabulary, MedDRA Version 20.1
Open or close this module Limitations and Caveats
The reported results include data collected up to the clinical data cut-off date of 29 September 2017.
Open or close this module More Information
Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact:
Name/Official Title:
 Medical Communications
Organization:
 Hoffmann-La Roche
Phone:
 800-821-8590
Email:
 genentech@druginfo.com
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