Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy. (SOLO-1)

• ClinicalTrials.gov Identifier: NCT01844986
• Recruitment Status: Active, not recruiting
• First Posted: May 3, 2013
• Results First Posted: July 9, 2019
• Last Update Posted: February 29, 2024
• Sponsor: AstraZeneca
• Collaborators: GOG Foundation; Myriad Genetic Laboratories, Inc.; Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): AstraZeneca

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Newly Diagnosed; Advanced Ovarian Cancer; FIGO Stage III-IV; BRCA Mutation; Complete Response; Partial Response; First Line Platinum Chemotherapy
• Intervention: Drug: Olaparib 300mg tablets
• Enrollment: 450

Participant Flow

Recruitment Details	Global Cohort: 391 randomised. First/Last patient randomised 03Sep2013/06Mar2015. China Cohort: 64 randomised. First/Last patient randomised 09Jan2015/22Mar2016. A total of 450 patients randomised (386 global cohort only, 64 China cohort (of which 5 included in global cohort)). Global Cohort used for hypotheses testing of study.
Pre-assignment Details	It was planned that approximately 344 women in the Global Cohort, and 53 women in the China Cohort, with BRCA mutated ovarian cancer patients who are in clinical complete or partial response following first line platinum based chemotherapy were to receive olaparib 300 mg bd or matching placebo in a 2:1 ratio.

Arm/Group Title	Olaparib 300mg Tablets	Placebo Tablets
Arm/Group Description	Taken orally twice daily	Taken orally twice daily
Period Title: Overall Study (Global Cohort)
Started [1]	260	131
Completed [2]	183	91
Not Completed	77	40
Reason Not Completed
Severe non-compliance to protocol	1	0
Withdrawal by Subject	21	14
Death	55	26
[1] (Randomised to study treatment); [2] (Ongoing study at time of PFS analysis DCO:17 May 2018)
Period Title: Overall Study (China Cohort)
Started [1]	44	20
Completed [2]	33	14
Not Completed	11	6
Reason Not Completed
Withdrawal by Subject	1	0
Death	10	6
[1] (Randomised to study treatment); [2] (Ongoing study at time of PFS analysis DCO:17 May 2018)

Baseline Characteristics

Arm/Group Title		Olaparib 300mg Tablets (Global Cohort & China Cohort)	Placebo Tablets (Global Cohort & China Cohort)	Total
Arm/Group Description		Taken orally twice daily	Taken orally twice daily	Total of all reporting groups
Overall Number of Baseline Participants		300	150	450
Baseline Analysis Population Description		Global Cohort (391 subjects): 260 Olaparib 131 Placebo China Cohort (64 subjects): 44 Olaparib 20 Placebo Included in both cohorts (5 subjects): 4 Olaparib 1 Placebo Total (450 subjects): 300 Olaparib 150 Placebo
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
Global Cohort	Number Analyzed	260 participants	131 participants	391 participants
		53.6 (9.38)	53.4 (9.79)	53.5 (9.51)
China Cohort	Number Analyzed	44 participants	20 participants	64 participants
		50.7 (7.27)	51.5 (7.95)	51.0 (7.44)
		[1] Measure Analysis Population Description: Each study is reported in a separate row. There were 4 participants who were in both the Global and China Olaparib Arm, and 1 participant in both the Global and China Placebo Arm.
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
Global Cohort	Number Analyzed	260 participants	131 participants	391 participants
	Female	260 100.0%	131 100.0%	391 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
China Cohort	Number Analyzed	44 participants	20 participants	64 participants
	Female	44 100.0%	20 100.0%	64 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Analysis Population Description: Each study is reported in a separate row. There were 4 participants who were in both the Global and China Olaparib Arm, and 1 participant in both the Global and China Placebo Arm.
Race (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
Global Cohort	Number Analyzed	260 participants	131 participants	391 participants
	American Indian or Alaska Native	0 0.0%	1 0.8%	1 0.3%
	Asian	39 15.0%	20 15.3%	59 15.1%
	Native Hawaiian or Other Pacific Islander	1 0.4%	1 0.8%	2 0.5%
	Black or African American	2 0.8%	2 1.5%	4 1.0%
	White	214 82.3%	106 80.9%	320 81.8%
	More than one race	1 0.4%	0 0.0%	1 0.3%
	Unknown or Not Reported	3 1.2%	1 0.8%	4 1.0%
China Cohort	Number Analyzed	44 participants	20 participants	64 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	44 100.0%	20 100.0%	64 100.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	0 0.0%	0 0.0%	0 0.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Analysis Population Description: Each study is reported in a separate row. There were 4 participants who were in both the Global and China Olaparib Arm, and 1 participant in both the Global and China Placebo Arm.
Response to previous platinum chemotherapy (as randomised) [1]; Measure Type: Count of Participants; Unit of measure: Participants
Global Cohort	Number Analyzed	260 participants	131 participants	391 participants
	Complete Response	213 81.9%	107 81.7%	320 81.8%
	Partial Response	47 18.1%	24 18.3%	71 18.2%
China Cohort	Number Analyzed	44 participants	20 participants	64 participants
	Complete Response	37 84.1%	18 90.0%	55 85.9%
	Partial Response	7 15.9%	2 10.0%	9 14.1%
		[1] Measure Analysis Population Description: Each study is reported in a separate row. There were 4 participants who were in both the Global and China Olaparib Arm, and 1 participant in both the Global and China Placebo Arm.

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
Description	To determine the efficacy by progression free survival (PFS) using investigator assessment according to modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy.
Time Frame	Radiologic scans performed at baseline then every 12 weeks up to 156 weeks, then every 24 weeks thereafter until objective radiological disease progression. DCO: 17 May 2018

Outcome Measure Data

Analysis Population Description

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) [Primary analysis] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).

Arm/Group Title	Olaparib 300mg Tablets (Global Cohort)	Placebo Tablets (Global Cohort)	Olaparib 300mg Tablets (China Cohort)	Placebo Tablets (China Cohort)
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	260	131	44	20
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (NA to NA)	13.8; (11.1 to 18.2)	NA [1]; (NA to NA)	9.3 [2]; (6.4 to NA)

[1]

Insufficient PFS events to estimate median, lower and upper confidence limit.

[2]

Insufficient PFS events to estimate upper confidence limit.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (Global Cohort), Placebo Tablets (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Determined using a log-rank test stratified by response to previous platinum chemotherapy
	Method	Regression, Cox
	Comments	Model includes a factor for response to previous platinum chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 95%; 0.23 to 0.41
	Estimation Comments	A hazard ratio < 1 favours olaparib

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (China Cohort), Placebo Tablets (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	Not applicable, due to small sample size. China cohort designed to provide descriptive analysis only.
	Method	Regression, Cox
	Comments	Model includes the stratification variable of response to first-line platinum chemotherapy as a covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; 0.23 to 0.97
	Estimation Comments	A hazard ratio < 1 favours olaparib

2. Secondary Outcome

Title	Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Overall Survival
Description	To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of overall survival (OS). Reports results of a pre-specified interim analysis; results for final OS analysis (235 OS events) anticipated 2029.
Time Frame	Assessed every 4 weeks until treatment discontinues (up to a max of 156 weeks), then as per protocol. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.

Outcome Measure Data

Analysis Population Description

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) [Primary analysis] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).

Arm/Group Title	Olaparib 300mg Tablets (Global Cohort)	Placebo Tablets (Global Cohort)	Olaparib 300mg Tablets (China Cohort)	Placebo Tablets (China Cohort)
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	260	131	44	20
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (NA to NA)	NA [1]; (NA to NA)	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Insufficient OS events to estimate median, lower and upper confidence limit.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (Global Cohort), Placebo Tablets (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8903
	Comments	Determined using a log-rank test stratified by response to previous platinum chemotherapy
	Method	Regression, Cox
	Comments	Model includes a factor for response to previous platinum chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.60 to 1.53
	Estimation Comments	A hazard ratio < 1 favours olaparib

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (China Cohort), Placebo Tablets (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	Not applicable, due to small sample size. China cohort designed to provide descriptive analysis only.
	Method	Regression, Cox
	Comments	Model includes the stratification variable of response to first-line platinum chemotherapy as a covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.29 to 2.28
	Estimation Comments	A hazard ratio < 1 favours olaparib

3. Secondary Outcome

Title	Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death
Description	To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time to earliest progression by RECIST or Cancer Antigen-125 (CA-125) or death
Time Frame	CA-125 performed at baseline + every 4 weeks. Radiologic scans performed at baseline + every 12 weeks up to 156 weeks, then every 24 weeks until objective radiological disease progression. DCO:17May2018

Outcome Measure Data

Analysis Population Description

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) [Primary analysis] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).

Arm/Group Title	Olaparib 300mg Tablets (Global Cohort)	Placebo Tablets (Global Cohort)	Olaparib 300mg Tablets (China Cohort)	Placebo Tablets (China Cohort)
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	260	131	44	20
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (NA to NA)	12.0; (10.8 to 16.6)	NA [1]; (NA to NA)	8.9 [2]; (6.4 to NA)

[1]

Insufficient events to estimate median, lower and upper confidence limit.

[2]

Insufficient events to estimate upper confidence limit.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (Global Cohort), Placebo Tablets (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Determined using a log-rank test stratified by response to previous platinum chemotherapy
	Method	Regression, Cox
	Comments	Model includes a factor for response to previous platinum chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 95%; 0.23 to 0.40
	Estimation Comments	A hazard ratio < 1 favours olaparib

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (China Cohort), Placebo Tablets (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	Not applicable due to small sample size. China cohort designed to provide descriptive analysis only.
	Method	Regression, Cox
	Comments	Model includes the stratification variable of response to first-line platinum chemotherapy as a covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.47
	Confidence Interval	(2-Sided) 95%; 0.23 to 0.99
	Estimation Comments	A hazard ratio <1 favours Olaparib.

4. Secondary Outcome

Title	Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression
Description	To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to second progression (PFS2)
Time Frame	Following first progression disease then assessed per local practice every 12 weeks until second progression.

Outcome Measure Data

Analysis Population Description

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) [Primary analysis] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).

Arm/Group Title	Olaparib 300mg Tablets (Global Cohort)	Placebo Tablets (Global Cohort)	Olaparib 300mg Tablets (China Cohort)	Placebo Tablets (China Cohort)
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	260	131	44	20
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (NA to NA)	41.9; (36.5 to 47.9)	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Insufficient PFS2 events to estimate median, lower and upper confidence limit.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (Global Cohort), Placebo Tablets (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0002
	Comments	Determined using a log-rank test stratified by response to previous platinum chemotherapy
	Method	Regression, Cox
	Comments	Model includes a factor for response to previous platinum chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; 0.35 to 0.72
	Estimation Comments	A hazard ratio < 1 favours olaparib

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (China Cohort), Placebo Tablets (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	Not applicable, due to small sample size. China cohort designed to provide descriptive analysis only.
	Method	Regression, Cox
	Comments	Model includes the stratification variable of response to first-line platinum chemotherapy as a covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; 0.23 to 1.35
	Estimation Comments	A hazard ratio <1 favours Olaparib.

5. Secondary Outcome

Title	Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O)
Description	To compare the effects of olaparib maintenance monotherapy compared to placebo on Health-related Quality of Life (HRQoL) as assessed by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy. The TOI ranges from 0-100 and a higher score indicates a higher HRQoL.
Time Frame	Questionnaires will be given to the patient at baseline, at Day 29 and then every 12 weeks for 156 weeks, then every 24 weeks or until the data cut off for the PFS analysis, change in TOI over 24 months reported

Outcome Measure Data

Analysis Population Description

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) with a baseline and post baseline TOI scores available.

Arm/Group Title	Olaparib 300mg Tablets (Global Cohort)	Placebo Tablets (Global Cohort)
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	260	131
Least Squares Mean (95% Confidence Interval); Unit of Measure: Scores on a scale
	0.30; (-0.717 to 1.318)	3.30; (1.839 to 4.758)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (Global Cohort), Placebo Tablets (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0010
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Fixed effects for treatment, visit and baseline TOI with the treatment by visit and baseline TOI by visit interaction. Random patient effect.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.00
	Confidence Interval	(2-Sided) 95%; -4.779 to -1.216
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to First Subsequent Therapy or Death (TFST)
Description	To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to first subsequent therapy or death (TFST). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).
Time Frame	Assessed every 12 weeks following treatment discontinuation. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.

Outcome Measure Data

Analysis Population Description

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) [Primary analysis] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).

Arm/Group Title	Olaparib 300mg Tablets (Global Cohort)	Placebo Tablets (Global Cohort)	Olaparib 300mg Tablets (China Cohort)	Placebo Tablets (China Cohort)
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	260	131	44	20
Median (95% Confidence Interval); Unit of Measure: Months
	51.8 [1]; (44.3 to NA)	15.1; (12.7 to 20.5)	34.3 [1]; (23.1 to NA)	10.3 [1]; (6.9 to NA)

[1]

Insufficient events to estimate upper confidence limit.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (Global Cohort), Placebo Tablets (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Determined using a log-rank test stratified by response to previous platinum chemotherapy
	Method	Regression, Cox
	Comments	Model includes a factor for response to previous platinum chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 95%; 0.22 to 0.40
	Estimation Comments	A hazard ratio < 1 favours olaparib

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (China Cohort), Placebo Tablets (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	Not applicable, due to small sample size. China cohort designed to provide descriptive analysis only.
	Method	Regression, Cox
	Comments	Model includes the stratification variable of response to first-line platinum chemotherapy as a covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; 0.29 to 1.23
	Estimation Comments	A hazard ratio <1 favours Olaparib.

7. Secondary Outcome

Title	Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Second Subsequent Therapy or Death (TSST)
Description	To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to second subsequent therapy or death (TSST). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).
Time Frame	Assessed every 12 weeks following treatment discontinuation. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.

Outcome Measure Data

Analysis Population Description

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) [Primary analysis] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).

Arm/Group Title	Olaparib 300mg Tablets (Global Cohort)	Placebo Tablets (Global Cohort)	Olaparib 300mg Tablets (China Cohort)	Placebo Tablets (China Cohort)
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	260	131	44	20
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (NA to NA)	40.7; (32.9 to 47.7)	NA [1]; (NA to NA)	27.4 [2]; (19.4 to NA)

[1]

Insufficient events to estimate median, lower and upper confidence limit.

[2]

Insufficient events to estimate upper confidence limit.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (Global Cohort), Placebo Tablets (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Determined using a log-rank test stratified by response to previous platinum chemotherapy
	Method	Regression, Cox
	Comments	Model includes a factor for response to previous platinum chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.45
	Confidence Interval	(2-Sided) 95%; 0.32 to 0.63
	Estimation Comments	A hazard ratio < 1 favours olaparib

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (China Cohort), Placebo Tablets (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	Not applicable, due to small sample size. China cohort designed to provide descriptive analysis only.
	Method	Regression, Cox
	Comments	Model includes the stratification variable of response to first-line platinum chemotherapy as a covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; 0.25 to 1.26
	Estimation Comments	A hazard ratio <1 favours Olaparib.

8. Secondary Outcome

Title	Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Study Treatment Discontinuation or Death (TDT)
Description	To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to study treatment discontinuation or death (TDT). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).
Time Frame	Time elapsed from randomization to study treatment discontinuation or death. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.

Outcome Measure Data

Analysis Population Description

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) [Primary analysis] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).

Arm/Group Title	Olaparib 300mg Tablets (Global Cohort)	Placebo Tablets (Global Cohort)	Olaparib 300mg Tablets (China Cohort)	Placebo Tablets (China Cohort)
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	260	131	44	20
Median (95% Confidence Interval); Unit of Measure: Months
	24.6; (24.0 to 24.8)	13.8; (11.2 to 16.4)	24.8; (14.2 to 24.9)	8.6; (5.9 to 24.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (Global Cohort), Placebo Tablets (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Determined using a log-rank test stratified by response to previous platinum chemotherapy
	Method	Regression, Cox
	Comments	Model includes a factor for response to previous platinum chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; 0.51 to 0.79
	Estimation Comments	A hazard ratio < 1 favours olaparib

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (China Cohort), Placebo Tablets (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	Not applicable, due to small sample size. China cohort designed to provide descriptive analysis only.
	Method	Regression, Cox
	Comments	Model includes the stratification variable of response to first-line platinum chemotherapy as a covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.47 to 1.42
	Estimation Comments	A hazard ratio <1 favours Olaparib.

9. Secondary Outcome

Title	Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS
Description	To assess efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and potential future BRCA mutation assays (gene sequencing and large rearrangement analysis)
Time Frame	Radiologic scans performed at baseline then every 12 weeks for the first 156 weeks, then every 24 weeks thereafter, assessed until disease progression. Analysis of data assessed up to a maximum of 54 months.

Outcome Measure Data

Analysis Population Description

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) and confirmed as Myriad gBRCAm.

Arm/Group Title	Olaparib 300mg Tablets (Global Cohort)	Placebo Tablets (Global Cohort)
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	253	130
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (NA to NA)	13.8; (11.1 to 18.2)

[1]

Insufficient PFS events to estimate median, lower and upper confidence limit.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (Global Cohort), Placebo Tablets (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Determined using a log-rank test stratified by response to previous platinum chemotherapy
	Method	Regression, Cox
	Comments	Model includes a factor for response to previous platinum chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 95%; 0.22 to 0.40
	Estimation Comments	A hazard ratio < 1 favours olaparib

Adverse Events

Time Frame	All adverse events (AEs) were collected from informed consent through treatment and safety follow-up period (30 days after study drug discontinued). Global cohort subjects were treated for an average of 1.7 years in Olaparib arm and 1.3 years in placebo arm. Subjects were followed up for all-cause mortality to end of study (no pre-specified max time). Global cohort subjects without a death reported were followed up for an average of 43.5 months in Olaparib arm and 42.5 months in placebo arm.
Adverse Event Reporting Description	Adverse events summaries showing subjects at risk are based on those subjects who received treatment. The summary of All cause mortality showing subjects at risk are based on those subjects who are randomised (irrespective of whether received treatment or not). Note 1 subject in Global cohort placebo arm was randomised but not treated.
Arm/Group Title	Olaparib 300mg Tablets (Global Cohort)		Placebo Tablets (Global Cohort)		Olaparib 300mg Tablets (China Cohort)		Placebo Tablets (China Cohort)
Arm/Group Description	Taken orally twice daily		Taken orally twice daily		Taken orally twice daily		Taken orally twice daily
All-Cause Mortality
	Olaparib 300mg Tablets (Global Cohort)		Placebo Tablets (Global Cohort)		Olaparib 300mg Tablets (China Cohort)		Placebo Tablets (China Cohort)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	55/260 (21.15%)		27/131 (20.61%)		10/44 (22.73%)		6/20 (30.00%)
Serious Adverse Events
	Olaparib 300mg Tablets (Global Cohort)		Placebo Tablets (Global Cohort)		Olaparib 300mg Tablets (China Cohort)		Placebo Tablets (China Cohort)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/260 (20.77%)		16/130 (12.31%)		13/44 (29.55%)		3/20 (15.00%)
Blood and lymphatic system disorders
Anaemia † 1	17/260 (6.54%)	36	0/130 (0.00%)	0	8/44 (18.18%)	10	0/20 (0.00%)	0
Bone marrow failure † 1	0/260 (0.00%)	0	0/130 (0.00%)	0	1/44 (2.27%)	1	0/20 (0.00%)	0
Febrile neutropenia † 1	2/260 (0.77%)	2	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Leukopenia † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	1/44 (2.27%)	1	0/20 (0.00%)	0
Lymphopenia † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Neutropenia † 1	2/260 (0.77%)	2	0/130 (0.00%)	0	2/44 (4.55%)	2	0/20 (0.00%)	0
Thrombocytopenia † 1	0/260 (0.00%)	0	0/130 (0.00%)	0	1/44 (2.27%)	1	0/20 (0.00%)	0
Splenic cyst † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	1/44 (2.27%)	1	0/20 (0.00%)	0
Cardiac disorders
Myocardial infarction † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	2/260 (0.77%)	2	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Diarrhoea † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Ileus † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Incarcerated umbilical hernia † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Intestinal obstruction † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Small intestinal obstruction † 1	2/260 (0.77%)	2	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Umbilical hernia † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Vomiting † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Gastritis † 1	0/260 (0.00%)	0	0/130 (0.00%)	0	1/44 (2.27%)	1	0/20 (0.00%)	0
Large intestine polyp † 1	0/260 (0.00%)	0	0/130 (0.00%)	0	1/44 (2.27%)	1	0/20 (0.00%)	0
Subileus † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
General disorders
Chills † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Incarcerated hernia † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Pyrexia † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Hepatobiliary disorders
Cholecystitis acute † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Infections and infestations
Cellulitis † 1	1/260 (0.38%)	1	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Cystitis † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Gastroenteritis † 1	0/260 (0.00%)	0	0/130 (0.00%)	0	1/44 (2.27%)	1	0/20 (0.00%)	0
Infected lymphocele † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Infection † 1	0/260 (0.00%)	0	0/130 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1
Lung infection † 1	0/260 (0.00%)	0	0/130 (0.00%)	0	1/44 (2.27%)	1	0/20 (0.00%)	0
Medical device site cellulitis † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Pneumonia † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Urinary tract infection † 1	3/260 (1.15%)	3	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Wound infection † 1	0/260 (0.00%)	0	1/130 (0.77%)	2	0/44 (0.00%)	0	0/20 (0.00%)	0
Appendicitis † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Sepsis † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Upper respiratory tract infection † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Urosepsis † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Viral infection † 1	2/260 (0.77%)	2	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Injury, poisoning and procedural complications
Thoracic vertebral fracture † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Accidental exposure to product by child † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Drug administration error † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Lumbar vertebral fracture † 1	0/260 (0.00%)	0	0/130 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1
Spinal compression fracture † 1	0/260 (0.00%)	0	0/130 (0.00%)	0	1/44 (2.27%)	1	0/20 (0.00%)	0
Stab wound † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Wound complication † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Investigations
Haemoglobin decreased † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Platelet count decreased † 1	1/260 (0.38%)	1	1/130 (0.77%)	1	1/44 (2.27%)	1	0/20 (0.00%)	0
Alanine aminotransferase increased † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Metabolism and nutrition disorders
Cell death † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Musculoskeletal and connective tissue disorders
Limb discomfort † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Rotator cuff syndrome † 1	2/260 (0.77%)	2	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Lip and/or oral cavity cancer † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Abdominal wall neoplasm benign † 1	0/260 (0.00%)	0	0/130 (0.00%)	0	1/44 (2.27%)	1	0/20 (0.00%)	0
Breast cancer female † 1	1/260 (0.38%)	1	3/130 (2.31%)	3	0/44 (0.00%)	0	0/20 (0.00%)	0
Intraductal proliferative breast lesion † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Thyroid cancer † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Thyroid cancer recurrent † 1	0/260 (0.00%)	0	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Nervous system disorders
Ataxia † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Headache † 1	1/260 (0.38%)	1	2/130 (1.54%)	2	0/44 (0.00%)	0	0/20 (0.00%)	0
Neuropathy peripheral † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Syncope † 1	2/260 (0.77%)	2	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Transient ischaemic attack † 1	2/260 (0.77%)	2	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Psychiatric disorders
Depression † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease † 1	0/260 (0.00%)	0	0/130 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1
Pneumonitis † 1	2/260 (0.77%)	2	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
Pulmonary embolism † 1	2/260 (0.77%)	3	0/130 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0
1 Term from vocabulary, MedDRA 21.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Olaparib 300mg Tablets (Global Cohort)		Placebo Tablets (Global Cohort)		Olaparib 300mg Tablets (China Cohort)		Placebo Tablets (China Cohort)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	253/260 (97.31%)		117/130 (90.00%)		43/44 (97.73%)		18/20 (90.00%)
Blood and lymphatic system disorders
Anaemia † 1	90/260 (34.62%)	156	12/130 (9.23%)	18	21/44 (47.73%)	44	3/20 (15.00%)	3
Bone marrow failure † 1	1/260 (0.38%)	1	0/130 (0.00%)	0	3/44 (6.82%)	4	0/20 (0.00%)	0
Leukopenia † 1	16/260 (6.15%)	33	5/130 (3.85%)	5	15/44 (34.09%)	64	2/20 (10.00%)	6
Neutropenia † 1	40/260 (15.38%)	84	9/130 (6.92%)	11	17/44 (38.64%)	68	1/20 (5.00%)	4
Thrombocytopenia † 1	21/260 (8.08%)	52	2/130 (1.54%)	4	13/44 (29.55%)	35	3/20 (15.00%)	4
Cardiac disorders
Palpitations † 1	12/260 (4.62%)	19	2/130 (1.54%)	2	3/44 (6.82%)	6	0/20 (0.00%)	0
Gastrointestinal disorders
Abdominal discomfort † 1	8/260 (3.08%)	10	2/130 (1.54%)	3	5/44 (11.36%)	8	1/20 (5.00%)	1
Abdominal distension † 1	18/260 (6.92%)	22	10/130 (7.69%)	10	2/44 (4.55%)	3	2/20 (10.00%)	4
Abdominal pain † 1	63/260 (24.23%)	86	25/130 (19.23%)	28	2/44 (4.55%)	4	2/20 (10.00%)	3
Abdominal pain lower † 1	8/260 (3.08%)	8	4/130 (3.08%)	4	1/44 (2.27%)	2	2/20 (10.00%)	2
Dyspepsia † 1	43/260 (16.54%)	50	16/130 (12.31%)	18	2/44 (4.55%)	2	1/20 (5.00%)	1
Nausea † 1	201/260 (77.31%)	412	49/130 (37.69%)	75	28/44 (63.64%)	49	5/20 (25.00%)	11
Stomatitis † 1	23/260 (8.85%)	37	3/130 (2.31%)	5	0/44 (0.00%)	0	0/20 (0.00%)	0
Toothache † 1	8/260 (3.08%)	8	4/130 (3.08%)	4	3/44 (6.82%)	3	2/20 (10.00%)	2
Abdominal pain upper † 1	46/260 (17.69%)	61	17/130 (13.08%)	22	9/44 (20.45%)	14	0/20 (0.00%)	0
Constipation † 1	72/260 (27.69%)	97	25/130 (19.23%)	30	8/44 (18.18%)	10	1/20 (5.00%)	1
Diarrhoea † 1	89/260 (34.23%)	205	32/130 (24.62%)	58	8/44 (18.18%)	12	4/20 (20.00%)	10
Gastric dilatation † 1	1/260 (0.38%)	1	1/130 (0.77%)	1	1/44 (2.27%)	1	2/20 (10.00%)	3
Mouth ulceration † 1	5/260 (1.92%)	11	0/130 (0.00%)	0	5/44 (11.36%)	6	0/20 (0.00%)	0
Vomiting † 1	104/260 (40.00%)	242	19/130 (14.62%)	26	18/44 (40.91%)	38	3/20 (15.00%)	4
General disorders
Fatigue † 1	106/260 (40.77%)	138	39/130 (30.00%)	48	16/44 (36.36%)	22	3/20 (15.00%)	3
Influenza like illness † 1	19/260 (7.31%)	29	11/130 (8.46%)	11	0/44 (0.00%)	0	0/20 (0.00%)	0
Oedema peripheral † 1	24/260 (9.23%)	32	9/130 (6.92%)	10	0/44 (0.00%)	0	0/20 (0.00%)	0
Asthenia † 1	63/260 (24.23%)	131	16/130 (12.31%)	20	3/44 (6.82%)	6	1/20 (5.00%)	2
Mucosal inflammation † 1	17/260 (6.54%)	27	1/130 (0.77%)	1	0/44 (0.00%)	0	0/20 (0.00%)	0
Pyrexia † 1	31/260 (11.92%)	40	12/130 (9.23%)	15	8/44 (18.18%)	8	2/20 (10.00%)	2
Infections and infestations
Cystitis † 1	15/260 (5.77%)	19	5/130 (3.85%)	8	0/44 (0.00%)	0	0/20 (0.00%)	0
Upper respiratory tract infection † 1	28/260 (10.77%)	36	12/130 (9.23%)	15	17/44 (38.64%)	20	6/20 (30.00%)	13
Influenza † 1	19/260 (7.31%)	24	3/130 (2.31%)	3	0/44 (0.00%)	0	0/20 (0.00%)	0
Nasopharyngitis † 1	27/260 (10.38%)	38	17/130 (13.08%)	37	5/44 (11.36%)	16	3/20 (15.00%)	15
Pharyngitis † 1	9/260 (3.46%)	11	3/130 (2.31%)	6	4/44 (9.09%)	5	0/20 (0.00%)	0
Sinusitis † 1	11/260 (4.23%)	12	8/130 (6.15%)	8	0/44 (0.00%)	0	0/20 (0.00%)	0
Urinary tract infection † 1	29/260 (11.15%)	52	8/130 (6.15%)	10	4/44 (9.09%)	4	2/20 (10.00%)	2
Investigations
Alanine aminotransferase increased † 1	9/260 (3.46%)	13	8/130 (6.15%)	8	6/44 (13.64%)	23	4/20 (20.00%)	7
Aspartate aminotransferase increased † 1	11/260 (4.23%)	13	6/130 (4.62%)	7	6/44 (13.64%)	15	3/20 (15.00%)	6
Blood creatinine increased † 1	21/260 (8.08%)	30	2/130 (1.54%)	4	2/44 (4.55%)	3	0/20 (0.00%)	0
Neutrophil count decreased † 1	20/260 (7.69%)	40	7/130 (5.38%)	14	7/44 (15.91%)	17	2/20 (10.00%)	6
Platelet count decreased † 1	8/260 (3.08%)	12	2/130 (1.54%)	4	6/44 (13.64%)	19	0/20 (0.00%)	0
Weight increased † 1	13/260 (5.00%)	15	12/130 (9.23%)	12	0/44 (0.00%)	0	0/20 (0.00%)	0
White blood cell count decreased † 1	16/260 (6.15%)	37	6/130 (4.62%)	9	10/44 (22.73%)	28	2/20 (10.00%)	9
Metabolism and nutrition disorders
Hypomagnesaemia † 1	13/260 (5.00%)	17	10/130 (7.69%)	15	0/44 (0.00%)	0	1/20 (5.00%)	1
Decreased appetite † 1	51/260 (19.62%)	68	13/130 (10.00%)	19	17/44 (38.64%)	22	1/20 (5.00%)	3
Hypokalaemia † 1	15/260 (5.77%)	24	3/130 (2.31%)	6	3/44 (6.82%)	10	3/20 (15.00%)	3
Musculoskeletal and connective tissue disorders
Arthralgia † 1	66/260 (25.38%)	88	35/130 (26.92%)	47	2/44 (4.55%)	2	3/20 (15.00%)	4
Back pain † 1	40/260 (15.38%)	50	16/130 (12.31%)	22	3/44 (6.82%)	6	2/20 (10.00%)	3
Myalgia † 1	28/260 (10.77%)	36	13/130 (10.00%)	17	2/44 (4.55%)	2	0/20 (0.00%)	0
Pain in extremity † 1	28/260 (10.77%)	34	11/130 (8.46%)	15	1/44 (2.27%)	4	2/20 (10.00%)	2
Muscle spasms † 1	17/260 (6.54%)	22	1/130 (0.77%)	1	1/44 (2.27%)	1	0/20 (0.00%)	0
Musculoskeletal pain † 1	16/260 (6.15%)	17	11/130 (8.46%)	13	1/44 (2.27%)	1	0/20 (0.00%)	0
Nervous system disorders
Dizziness † 1	51/260 (19.62%)	68	20/130 (15.38%)	23	8/44 (18.18%)	10	6/20 (30.00%)	16
Dysgeusia † 1	68/260 (26.15%)	92	5/130 (3.85%)	6	3/44 (6.82%)	4	0/20 (0.00%)	0
Headache † 1	58/260 (22.31%)	109	30/130 (23.08%)	40	7/44 (15.91%)	9	3/20 (15.00%)	10
Hypoaesthesia † 1	5/260 (1.92%)	6	2/130 (1.54%)	3	4/44 (9.09%)	4	0/20 (0.00%)	0
Neuropathy peripheral † 1	15/260 (5.77%)	15	7/130 (5.38%)	9	0/44 (0.00%)	0	0/20 (0.00%)	0
Psychiatric disorders
Anxiety † 1	15/260 (5.77%)	15	11/130 (8.46%)	11	1/44 (2.27%)	1	0/20 (0.00%)	0
Depression † 1	12/260 (4.62%)	14	13/130 (10.00%)	15	2/44 (4.55%)	2	0/20 (0.00%)	0
Insomnia † 1	27/260 (10.38%)	31	16/130 (12.31%)	20	3/44 (6.82%)	3	3/20 (15.00%)	5
Respiratory, thoracic and mediastinal disorders
Cough † 1	42/260 (16.15%)	57	28/130 (21.54%)	37	5/44 (11.36%)	6	2/20 (10.00%)	4
Dyspnoea † 1	39/260 (15.00%)	53	7/130 (5.38%)	7	0/44 (0.00%)	0	0/20 (0.00%)	0
Oropharyngeal pain † 1	21/260 (8.08%)	26	12/130 (9.23%)	15	3/44 (6.82%)	3	2/20 (10.00%)	2
Skin and subcutaneous tissue disorders
Rash † 1	16/260 (6.15%)	23	11/130 (8.46%)	11	2/44 (4.55%)	4	1/20 (5.00%)	1
Vascular disorders
Hot flush † 1	17/260 (6.54%)	25	11/130 (8.46%)	12	1/44 (2.27%)	1	0/20 (0.00%)	0
Hypertension † 1	9/260 (3.46%)	18	12/130 (9.23%)	17	1/44 (2.27%)	1	0/20 (0.00%)	0
1 Term from vocabulary, MedDRA 21.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

The data presented based on the March DCO (17 May 2018) are not the final analyses for OS, TFST, TSST, and TDT. Further analyses of these (numbered as endpoints 2, 6, 7 and 8 in Outcome Measures section) will be performed as planned in the protocol and SAP when the pre-specified number of OS events are achieved.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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

Results Point of Contact

• Name/Title: Elizabeth Lowe
• Organization: AstraZeneca
• Phone: +1 302 885 1180
• EMail: ClinicalTrialTransparency@astrazeneca.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

DiSilvestro P, Banerjee S, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Oza A, Gonzalez-Martin A, Aghajanian C, Bradley W, Mathews C, Liu J, McNamara J, Lowe ES, Ah-See ML, Moore KN; SOLO1 Investigators. Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial. J Clin Oncol. 2023 Jan 20;41(3):609-617. doi: 10.1200/JCO.22.01549. Epub 2022 Sep 9.

Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.

Banerjee S, Moore KN, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Oza A, Gonzalez-Martin A, Aghajanian C, Bradley WH, Holmes E, Lowe ES, DiSilvestro P. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1721-1731. doi: 10.1016/S1470-2045(21)00531-3. Epub 2021 Oct 26. Erratum In: Lancet Oncol. 2021 Dec;22(12):e539.

Friedlander M, Moore KN, Colombo N, Scambia G, Kim BG, Oaknin A, Lisyanskaya A, Sonke GS, Gourley C, Banerjee S, Oza A, Gonzalez-Martin A, Aghajanian C, Bradley WH, Liu J, Mathews C, Selle F, Lortholary A, Lowe ES, Hettle R, Flood E, Parkhomenko E, DiSilvestro P. Patient-centred outcomes and effect of disease progression on health status in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation receiving maintenance olaparib or placebo (SOLO1): a randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):632-642. doi: 10.1016/S1470-2045(21)00098-X. Epub 2021 Apr 13.

Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, Gonzalez-Martin A, Aghajanian C, Bradley W, Mathews C, Liu J, Lowe ES, Bloomfield R, DiSilvestro P. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2018 Dec 27;379(26):2495-2505. doi: 10.1056/NEJMoa1810858. Epub 2018 Oct 21.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01844986
• Other Study ID Numbers: D0818C00001; 2013-001551-13 ( EudraCT Number )
• First Submitted: April 30, 2013
• First Posted: May 3, 2013
• Results First Submitted: May 9, 2019
• Results First Posted: July 9, 2019
• Last Update Posted: February 29, 2024