Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy

• ClinicalTrials.gov Identifier: NCT01874353
• Recruitment Status: Active, not recruiting
• First Posted: June 11, 2013
• Results First Posted: February 7, 2018
• Last Update Posted: April 1, 2024
• Sponsor: AstraZeneca
• Collaborators: European Network of Gynaecological Oncological Trial Groups (ENGOT); 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: Platinum Sensitive; BRCA Mutated; Relapsed Ovarian Cancer; Following Complete or Partial Response to Platinum Based Chemotherapy
• Interventions: Drug: Olaparib 300mg tablets; Drug: Placebo to match olaparib 300mg
• Enrollment: 327

Participant Flow

Recruitment Details

Global Cohort: First patient screened: 03 Sep 2013; last patient screened on 21 Nov 2014. 602 patients screened across 119 centres in 16 countries; 295 were randomized. Results are reported for analysis of PFS (DCO: 19 Sep 2016) and OS (DCO: 03 Feb 2020). China Cohort: First patient enrolled: 07 Apr 2015; last patient enrolled: 30 Oct 2015. 127 patients screened across 16 sites; 32 were randomized. Results are reported for analysis of PFS (DCO: 16 Jan 2017) and OS (DCO: 03 Feb 2020).

Pre-assignment Details

It was planned that approximately 264 women from the Global Cohort and 33 women from the China Cohort, with BRCA mutated relapsed ovarian cancer who are in complete or partial response following platinum based chemotherapy, were to receive olaparib 300 mg bd or matching placebo in a 2:1 ratio.

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
Period Title: Overall Study
Started	196	99	22	10
Completed	69	26	7	3
Not Completed	127	73	15	7
Reason Not Completed
One patient was unblinded and one patient was randomised in error	2	0	0	0
Lost to Follow-up	2	2	2	0
Death	110	60	13	7
Withdrawal by Subject	13	11	0	0

Baseline Characteristics

Arm/Group Title		Olaparib 300mg Tablets	Placebo Tablets	Total
Arm/Group Description		Taken orally twice daily	Taken orally twice daily	Total of all reporting groups
Overall Number of Baseline Participants		218	109	327
Baseline Analysis Population Description		Global Cohort: 196 Olaparib, 99 Placebo China Cohort: 22 Olaparib, 10 Placebo
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
Global Cohort	Number Analyzed	196 participants	99 participants	295 participants
		57.0 (9.2)	56.6 (8.9)	56.9 (9.09)
China Cohort	Number Analyzed	22 participants	10 participants	32 participants
		50.6 (8.42)	47.4 (9.29)	49.6 (8.68)
		[1] Measure Analysis Population Description: There are 196 Olaparib patients in the Global Cohort and 22 in the China Cohort (Total = 218). There are 99 Placebo patients in the Global Cohort and 10 in the China Cohort (Total = 109)
Age, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants
Global Cohort	Number Analyzed	196 participants	99 participants	295 participants
	<50	38 19.4%	25 25.3%	63 21.4%
	>=50-<65	118 60.2%	52 52.5%	170 57.6%
	>=65	40 20.4%	22 22.2%	62 21.0%
China Cohort	Number Analyzed	22 participants	10 participants	32 participants
	<50	11 50.0%	7 70.0%	18 56.3%
	>=50-<65	10 45.5%	2 20.0%	12 37.5%
	>=65	1 4.5%	1 10.0%	2 6.3%
		[1] Measure Analysis Population Description: There are 196 Olaparib patients in the Global Cohort and 22 in the China Cohort (Total = 218). There are 99 Placebo patients in the Global Cohort and 10 in the China Cohort (Total = 109)
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
Global Cohort	Number Analyzed	196 participants	99 participants	295 participants
	Female	196 100.0%	99 100.0%	295 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
China Cohort	Number Analyzed	22 participants	10 participants	32 participants
	Female	22 100.0%	10 100.0%	32 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Analysis Population Description: There are 196 Olaparib patients in the Global Cohort and 22 in the China Cohort (Total = 218). There are 99 Placebo patients in the Global Cohort and 10 in the China Cohort (Total = 109)
Ethnicity (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
Global Cohort	Number Analyzed	196 participants	99 participants	295 participants
	Hispanic or Latino	10 5.1%	1 1.0%	11 3.7%
	Not Hispanic or Latino	186 94.9%	98 99.0%	284 96.3%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
China Cohort	Number Analyzed	22 participants	10 participants	32 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	22 100.0%	10 100.0%	32 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Analysis Population Description: There are 196 Olaparib patients in the Global Cohort and 22 in the China Cohort (Total = 218). There are 99 Placebo patients in the Global Cohort and 10 in the China Cohort (Total = 109)
Race/Ethnicity, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants
Global Cohort	Number Analyzed	196 participants	99 participants	295 participants
	WHITE	173 88.3%	91 91.9%	264 89.5%
	BLACK OR AFRICAN AMERICAN	1 0.5%	0 0.0%	1 0.3%
	AMERICAN INDIAN OR ALASKA NATIVE	0 0.0%	0 0.0%	0 0.0%
	ASIAN	22 11.2%	7 7.1%	29 9.8%
	NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	0 0.0%	0 0.0%	0 0.0%
	OTHER	0 0.0%	1 1.0%	1 0.3%
China Cohort	Number Analyzed	22 participants	10 participants	32 participants
	WHITE	0 0.0%	0 0.0%	0 0.0%
	BLACK OR AFRICAN AMERICAN	0 0.0%	0 0.0%	0 0.0%
	AMERICAN INDIAN OR ALASKA NATIVE	0 0.0%	0 0.0%	0 0.0%
	ASIAN	22 100.0%	10 100.0%	32 100.0%
	NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	0 0.0%	0 0.0%	0 0.0%
	OTHER	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Analysis Population Description: There are 196 Olaparib patients in the Global Cohort and 22 in the China Cohort (Total = 218). There are 99 Placebo patients in the Global Cohort and 10 in the China Cohort (Total = 109)

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 relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy.
Time Frame	Radiologic scans performed at baseline then every ~12 weeks up to 72 weeks, then every ~ 24 weeks thereafter until objective radiological disease progression. Assessed until 19 Sep 2016 DCO (16 Jan 2017 DCO for China Cohort); up to a maximum of 36 months.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment, excluding China [Primary analysis] China Full Analysis Set (FAS) includes all patients who were randomised at sites in China.

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	196	99	22	10
Median (95% Confidence Interval); Unit of Measure: Months
	19.1; (16.3 to 25.7)	5.5; (5.2 to 5.8)	13.8; (6.5 to 16.6)	5.5 [1]; (2.7 to NA)

[1]

Insufficient PFS events to estimate upper 95% CI

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 or Other (legacy)
	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 and time to disease progression in the penultimate platinum based chemotherapy prior to enrolment
	Method	Regression, Cox
	Comments	Model includes factors for response to previous platinum chemotherapy and time to disease progression in the penultimate platinum based chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 95%; 0.22 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 or Other (legacy)
	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 a treatment factor only
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95%; 0.17 to 1.19
	Estimation Comments	A hazard ratio < 1 favours olaparib

2. Secondary Outcome

Title	Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Overall Survival
Description	To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy by assessment of overall survival (OS).
Time Frame	Survival assessed every 4 weeks until treatment discontinues, then every 12 weeks. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment (excluding China) China Full Analysis Set (FAS) includes all patients who were randomised at sites in China.

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	196	99	22	10
Median (95% Confidence Interval); Unit of Measure: Months
	51.7; (41.5 to 59.1)	38.8; (31.4 to 48.6)	41.7 [1]; (17.6 to NA)	36.4 [1]; (13.2 to NA)

[1]

Insufficient OS events to estimate upper 95% CI

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 or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0537
	Comments	Determined using a log-rank test stratified by response to previous platinum chemotherapy and time to disease progression in the penultimate platinum based chemotherapy prior to enrolment
	Method	Regression, Cox
	Comments	Model includes factors for response to previous platinum chemotherapy and time to disease progression in the penultimate platinum based chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.00
	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 or Other (legacy)
	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 a treatment factor only
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.38 to 2.49
	Estimation Comments	A hazard ratio <1 favours olaparib

3. Secondary Outcome

Title	Efficacy in Patients Following 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 relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy by assessment of time to earliest progression by RECIST or CA-125 or death.
Time Frame	CA-125 at baseline then every 4 wks. Radiologic scans at baseline then every ~12 wks up to 72 wks, then every ~ 24 wks until objective radiological disease progression. Assessed until 19Sep2016 DCO (16Jan2017 DCO for China Cohort); up to a max of 36 mths.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment (excluding China).

China Full Analysis Set (FAS) includes all patients who were randomised at sites in China.

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	196	99	22	10
Median (95% Confidence Interval); Unit of Measure: Months
	16.9; (14.6 to 22.3)	4.9; (3.7 to 5.6)	12.9; (5.9 to 14.0)	3.7; (1.0 to 7.4)

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 or Other (legacy)
	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 and time to disease progression in the penultimate platinum based chemotherapy prior to enrolment
	Method	Regression, Cox
	Comments	Model includes factors for response to previous platinum chemotherapy and time to disease progression in the penultimate platinum based 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 or Other (legacy)
	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 a treatment factor only
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.41
	Confidence Interval	(2-Sided) 95%; 0.18 to 1.03
	Estimation Comments	A hazard ratio <1 favours olaparib

4. Secondary Outcome

Title	Efficacy in Patients Following 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 relapsed ovarian cancer patients who are in complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization up to second progression
Time Frame	Scans at baseline then every 12 wks for 72 wks, then every 24 wks until first progression. Assessments then per local practice every 12 wks until second progression. Assessed until 19Sep2016 DCO (16Jan2017 DCO for China Cohort); up to a max of 36 mths

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment (excluding China).

China Full Analysis Set (FAS) includes all patients who were randomised at sites in China.

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	196	99	22	10
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (24.1 to NA)	18.4; (15.4 to 22.8)	NA [2]; (NA to NA)	17.3; (6.0 to 17.3)

[1]

Insufficient PFS2 events to estimate upper 95% CI

[2]

Insufficient PFS2 events to estimate median and 95% CI

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 or Other (legacy)
	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 and time to disease progression in the penultimate platinum based chemotherapy prior to enrolment
	Method	Regression, Cox
	Comments	Model includes factors for response to previous platinum chemotherapy and time to disease progression in the penultimate platinum based chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; 0.34 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 or Other (legacy)
	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 treatment factor only
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.22 to 3.97
	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 relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy. The TOI ranges from 0-100 and a higher score indicates a higher HRQoL.
Time Frame	Questionnaires completed by patient at baseline, Day 29 and then every 12 weeks for 12 months. Assessed until 19 Sep 2016 DCO.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment (excluding China) with a baseline and post baseline TOI score available [This endpoint was not assessed in the China Cohort]

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	185	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Change in TOI over 12 months
	-2.90; (-4.131 to -1.673)	-2.87; (-4.643 to -1.097)

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 or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9765
	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	-0.03
	Confidence Interval	(2-Sided) 95%; -2.191 to 2.126
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Efficacy of Olaparib by 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 randomization to first subsequent therapy or death (TFST).
Time Frame	Time elapsed from randomization to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment (excluding China).

China Full Analysis Set (FAS) includes all patients who were randomised at sites in China.

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	196	99	22	10
Median (95% Confidence Interval); Unit of Measure: Months
	27.4; (22.6 to 31.1)	7.2; (6.3 to 8.5)	13.9; (9.1 to 15.9)	5.5; (1.4 to 18.4)

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 or Other (legacy)
	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 and time to disease progression in the penultimate platinum based chemotherapy prior to enrolment
	Method	Regression, Cox
	Comments	Model includes factors for response to previous platinum chemotherapy and time to disease progression in the penultimate platinum based chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; 0.28 to 0.48
	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 or Other (legacy)
	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 a treatment factor only
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.47
	Confidence Interval	(2-Sided) 95%; 0.21 to 1.08
	Estimation Comments	A hazard ratio < 1 favours olaparib

7. Secondary Outcome

Title	Efficacy of Olaparib by 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 randomization to second subsequent therapy or death (TSST).
Time Frame	Time elapsed from randomization to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment (excluding China).

China Full Analysis Set (FAS) includes all patients who were randomised at sites in China.

Arm/Group Title	Olaparib 300mg Tablets (Global Cohort)	Placebo Tablets (Global Cohort)	Olaparib 300mg Tablets (ChinaCohort)	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	196	99	22	10
Median (95% Confidence Interval); Unit of Measure: Months
	35.8; (29.4 to 43.9)	18.9; (15.5 to 21.5)	19.0; (10.1 to 32.8)	26.4; (6.3 to 36.0)

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 or Other (legacy)
	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 and time to disease progression in the penultimate platinum based chemotherapy prior to enrolment
	Method	Regression, Cox
	Comments	Model includes factors for response to previous platinum chemotherapy and time to disease progression in the penultimate platinum based chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; 0.39 to 0.68
	Estimation Comments	A hazard ratio < 1 favours olaparib

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets (ChinaCohort), Placebo Tablets (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	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 included treatment factor only
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.37 to 1.85
	Estimation Comments	A hazard ratio < 1 favours olaparib

8. Secondary Outcome

Title	Efficacy of Olaparib by 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 randomization to study treatment discontinuation or death (TDT).
Time Frame	Time elapsed from randomization to study treatment discontinuation or death. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment (excluding China).

China Full Analysis Set (FAS) includes all patients who were randomised at sites in China.

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	196	99	22	10
Median (95% Confidence Interval); Unit of Measure: Months
	19.4; (14.9 to 25.9)	5.6; (5.0 to 6.8)	13.4; (6.3 to 16.5)	4.7; (1.3 to 11.1)

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 or Other (legacy)
	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 and time to disease progression in the penultimate platinum based chemotherapy prior to enrolment
	Method	Regression, Cox
	Comments	Model includes factors for response to previous platinum chemotherapy and time to disease progression in the penultimate platinum based chemotherapy
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; 0.28 to 0.49
	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 or Other (legacy)
	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 a treatment factor only
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.45
	Confidence Interval	(2-Sided) 95%; 0.20 to 1.04
	Estimation Comments	A hazard ratio < 1 favours the Olaparib arm

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 future BRCA mutation assays (gene sequencing and large rearrangement analysis).
Time Frame	Radiologic scans performed at baseline then every ~12 weeks for the first 72 weeks, then every ~24 weeks thereafter, assessed until disease progression. Assessed until 19 Sep 2016 DCO.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment (excluding China) and confirmed as Myriad gBRCAm [This endpoint was not assessed in the China Cohort]

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	190	96
Median (95% Confidence Interval); Unit of Measure: Months
	19.3; (16.5 to 27.3)	5.5; (5.0 to 5.8)

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 or Other (legacy)
	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 and time to disease progression in the penultimate platinum based chemotherapy prior to enrolment
	Method	Regression, Cox
	Comments	Model includes factors for response to previous platinum chemotherapy and time to disease progression in the penultimate platinum based 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

10. Secondary Outcome

Title	To Determine the Exposure to Olaparib by Pharmacokinetic Analysis
Description	To determine the exposure to olaparib in patients receiving olaparib maintenance monotherapy
Time Frame	Pharmacokinetics sampling to be performed in a subset of patients. Sampling times: Day 1 pre-dose & 1 hour; Day 15 pre-dose & 1 hour; Day 29 pre-dose. Assessed until 19 Sep 2016 DCO.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set - all patients who receive study treatment as per protocol, do not violate or deviate from the protocol in ways that would significantly affect the PK analyses and have valid PK data.

The PK Analysis Set is a subset of the Global FAS; PK analysis was not performed in the China Cohort.

Arm/Group Title	Olaparib 300mg Tablets
Arm/Group Description:	Taken orally twice daily
Overall Number of Participants Analyzed	93
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: mcg/mL
Day 1 - Pre-dose	NA [1]; (NA%)
Day 1 - 1 hour	3.26; (312.2%)
Day 15 - Pre-dose	0.92; (95.5%)
Day 15 - 1 hour	5.12; (61.8%)
Day 29 - Pre-dose	0.94; (179.0%)

[1]

Prior to receiving olaparib so not calculated

Adverse Events

Time Frame	Includes adverse events with an onset date on or after the date of first dose and up to and including 30 days following the date of last dose of olaparib/placebo.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Olaparib 300 Tablets (Global Cohort)		Placebo Tablets (Global Cohort)		Olaparib 300 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 300 Tablets (Global Cohort)		Placebo Tablets (Global Cohort)		Olaparib 300 Tablets (China Cohort)		Placebo Tablets (China Cohort)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	116/196 (59.18%)		65/99 (65.66%)		13/22 (59.09%)		7/10 (70.00%)
Serious Adverse Events
	Olaparib 300 Tablets (Global Cohort)		Placebo Tablets (Global Cohort)		Olaparib 300 Tablets (China Cohort)		Placebo Tablets (China Cohort)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/195 (25.64%)		8/99 (8.08%)		5/22 (22.73%)		1/10 (10.00%)
Blood and lymphatic system disorders
Anaemia † 1	8/195 (4.10%)	13	0/99 (0.00%)	0	2/22 (9.09%)	2	0/10 (0.00%)	0
Febrile neutropenia † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Neutropenia † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	1/22 (4.55%)	1	0/10 (0.00%)	0
Leukopenia † 1	0/195 (0.00%)	0	0/99 (0.00%)	0	1/22 (4.55%)	1	0/10 (0.00%)	0
Cardiac disorders
Coronary artery stenosis † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Myocardial infarction † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Pericarditis † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Gastrointestinal disorders
Abdominal hernia † 1	0/195 (0.00%)	0	1/99 (1.01%)	1	0/22 (0.00%)	0	0/10 (0.00%)	0
Abdominal pain † 1	4/195 (2.05%)	5	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Ascites † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Dysphagia † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Food poisoning † 1	0/195 (0.00%)	0	0/99 (0.00%)	0	1/22 (4.55%)	1	0/10 (0.00%)	0
Intestinal obstruction † 1	4/195 (2.05%)	5	1/99 (1.01%)	1	0/22 (0.00%)	0	0/10 (0.00%)	0
Nausea † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Small intestinal obstruction † 1	0/195 (0.00%)	0	2/99 (2.02%)	3	0/22 (0.00%)	0	0/10 (0.00%)	0
Subileus † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Constipation † 1	0/195 (0.00%)	0	2/99 (2.02%)	2	0/22 (0.00%)	0	0/10 (0.00%)	0
Enteritis † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Vomiting † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
General disorders
Malaise † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Oedema peripheral † 1	1/195 (0.51%)	2	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Pyrexia † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Fatigue † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Hepatobiliary disorders
Cholecystitis † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Immune system disorders
Anaphylactic reaction † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Hypersensitivity † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Infections and infestations
Gastroenteritis † 1	0/195 (0.00%)	0	0/99 (0.00%)	0	0/22 (0.00%)	0	1/10 (10.00%)	1
Neutropenic sepsis † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Pneumonia † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Urinary tract infection † 1	2/195 (1.03%)	2	1/99 (1.01%)	1	0/22 (0.00%)	0	0/10 (0.00%)	0
Device related infection † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Spinal cord infection † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Injury, poisoning and procedural complications
Incisional hernia † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Post procedural complication † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Post procedural fistula † 1	0/195 (0.00%)	0	1/99 (1.01%)	1	0/22 (0.00%)	0	0/10 (0.00%)	0
Investigations
Blood creatine phosphokinase increased † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
White blood cell count decreased † 1	0/195 (0.00%)	0	0/99 (0.00%)	0	1/22 (4.55%)	1	0/10 (0.00%)	0
Amylase increased † 1	0/195 (0.00%)	0	1/99 (1.01%)	1	0/22 (0.00%)	0	0/10 (0.00%)	0
Blood creatinine increased † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Haemoglobin decreased † 1	0/195 (0.00%)	0	0/99 (0.00%)	0	1/22 (4.55%)	3	0/10 (0.00%)	0
Neutrophil count decreased † 1	0/195 (0.00%)	0	0/99 (0.00%)	0	1/22 (4.55%)	1	0/10 (0.00%)	0
Metabolism and nutrition disorders
Hypokalaemia † 1	0/195 (0.00%)	0	1/99 (1.01%)	1	0/22 (0.00%)	0	0/10 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	0/195 (0.00%)	0	1/99 (1.01%)	1	0/22 (0.00%)	0	0/10 (0.00%)	0
Fibromyalgia † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Muscular weakness † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Osteoarthritis † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Lymphoma † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Myelodysplastic syndrome † 1	4/195 (2.05%)	4	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Squamous cell carcinoma † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Squamous cell carcinoma of the tongue † 1	1/195 (0.51%)	2	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Acute myeloid leukaemia † 1	3/195 (1.54%)	3	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Adenocarcinoma gastric † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Gastric cancer † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Gastrointestinal carcinoma † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Invasive ductal breast carcinoma † 1	0/195 (0.00%)	0	1/99 (1.01%)	1	0/22 (0.00%)	0	0/10 (0.00%)	0
Plasma cell myeloma † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Squamous cell carcinoma of skin † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Thyroid cancer † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Renal and urinary disorders
Haematuria † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough † 1	2/195 (1.03%)	2	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Dyspnoea † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Pneumonitis † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Skin and subcutaneous tissue disorders
Drug reaction with eosinophilia and systemic symptoms † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Vascular disorders
Deep vein thrombosis † 1	3/195 (1.54%)	3	1/99 (1.01%)	1	0/22 (0.00%)	0	0/10 (0.00%)	0
1 Term from vocabulary, MedDRA 22.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Olaparib 300 Tablets (Global Cohort)		Placebo Tablets (Global Cohort)		Olaparib 300 Tablets (China Cohort)		Placebo Tablets (China Cohort)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	192/195 (98.46%)		91/99 (91.92%)		21/22 (95.45%)		10/10 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	83/195 (42.56%)	149	9/99 (9.09%)	9	7/22 (31.82%)	14	0/10 (0.00%)	0
Leukopenia † 1	21/195 (10.77%)	35	1/99 (1.01%)	1	4/22 (18.18%)	4	0/10 (0.00%)	0
Neutropenia † 1	27/195 (13.85%)	47	5/99 (5.05%)	12	5/22 (22.73%)	7	0/10 (0.00%)	0
Thrombocytopenia † 1	18/195 (9.23%)	22	3/99 (3.03%)	3	3/22 (13.64%)	5	2/10 (20.00%)	3
Gastrointestinal disorders
Abdominal distension † 1	13/195 (6.67%)	13	7/99 (7.07%)	7	3/22 (13.64%)	4	3/10 (30.00%)	3
Abdominal pain † 1	53/195 (27.18%)	90	31/99 (31.31%)	34	3/22 (13.64%)	6	0/10 (0.00%)	0
Abdominal pain upper † 1	24/195 (12.31%)	27	13/99 (13.13%)	14	3/22 (13.64%)	3	1/10 (10.00%)	1
Constipation † 1	46/195 (23.59%)	65	23/99 (23.23%)	30	1/22 (4.55%)	3	1/10 (10.00%)	1
Diarrhoea † 1	67/195 (34.36%)	128	20/99 (20.20%)	28	4/22 (18.18%)	4	0/10 (0.00%)	0
Dry mouth † 1	12/195 (6.15%)	19	4/99 (4.04%)	4	0/22 (0.00%)	0	0/10 (0.00%)	0
Flatulence † 1	10/195 (5.13%)	11	1/99 (1.01%)	1	0/22 (0.00%)	0	0/10 (0.00%)	0
Gastrooesophageal reflux disease † 1	15/195 (7.69%)	15	4/99 (4.04%)	4	1/22 (4.55%)	1	0/10 (0.00%)	0
Mouth ulceration † 1	5/195 (2.56%)	19	1/99 (1.01%)	5	2/22 (9.09%)	5	0/10 (0.00%)	0
Stomatitis † 1	20/195 (10.26%)	39	6/99 (6.06%)	7	1/22 (4.55%)	1	0/10 (0.00%)	0
Vomiting † 1	77/195 (39.49%)	153	20/99 (20.20%)	27	8/22 (36.36%)	17	1/10 (10.00%)	1
Anal fissure † 1	2/195 (1.03%)	3	1/99 (1.01%)	1	0/22 (0.00%)	0	1/10 (10.00%)	1
Dyspepsia † 1	29/195 (14.87%)	43	9/99 (9.09%)	9	0/22 (0.00%)	0	0/10 (0.00%)	0
Nausea † 1	148/195 (75.90%)	290	35/99 (35.35%)	48	18/22 (81.82%)	33	1/10 (10.00%)	3
General disorders
Fatigue † 1	75/195 (38.46%)	91	15/99 (15.15%)	22	7/22 (31.82%)	11	2/10 (20.00%)	4
Influenza like illness † 1	15/195 (7.69%)	18	1/99 (1.01%)	1	0/22 (0.00%)	0	0/10 (0.00%)	0
Malaise † 1	5/195 (2.56%)	5	2/99 (2.02%)	2	2/22 (9.09%)	2	0/10 (0.00%)	0
Asthenia † 1	62/195 (31.79%)	107	27/99 (27.27%)	29	2/22 (9.09%)	2	0/10 (0.00%)	0
Mucosal inflammation † 1	13/195 (6.67%)	18	3/99 (3.03%)	4	0/22 (0.00%)	0	0/10 (0.00%)	0
Oedema peripheral † 1	17/195 (8.72%)	20	7/99 (7.07%)	8	0/22 (0.00%)	0	1/10 (10.00%)	1
Pyrexia † 1	28/195 (14.36%)	39	6/99 (6.06%)	9	1/22 (4.55%)	1	1/10 (10.00%)	2
Hepatobiliary disorders
Hepatic function abnormal † 1	0/195 (0.00%)	0	0/99 (0.00%)	0	0/22 (0.00%)	0	1/10 (10.00%)	1
Infections and infestations
Bronchitis † 1	13/195 (6.67%)	14	2/99 (2.02%)	2	0/22 (0.00%)	0	0/10 (0.00%)	0
Herpes zoster † 1	4/195 (2.05%)	9	2/99 (2.02%)	2	0/22 (0.00%)	0	1/10 (10.00%)	1
Nasopharyngitis † 1	25/195 (12.82%)	48	11/99 (11.11%)	14	2/22 (9.09%)	3	1/10 (10.00%)	1
Cystitis † 1	15/195 (7.69%)	27	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Influenza † 1	17/195 (8.72%)	19	6/99 (6.06%)	6	0/22 (0.00%)	0	0/10 (0.00%)	0
Oral herpes † 1	11/195 (5.64%)	14	3/99 (3.03%)	5	0/22 (0.00%)	0	0/10 (0.00%)	0
Sinusitis † 1	11/195 (5.64%)	13	4/99 (4.04%)	6	0/22 (0.00%)	0	0/10 (0.00%)	0
Upper respiratory tract infection † 1	17/195 (8.72%)	25	6/99 (6.06%)	10	7/22 (31.82%)	14	2/10 (20.00%)	5
Urinary tract infection † 1	18/195 (9.23%)	28	9/99 (9.09%)	12	1/22 (4.55%)	1	0/10 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	10/195 (5.13%)	15	4/99 (4.04%)	4	3/22 (13.64%)	3	2/10 (20.00%)	4
Aspartate aminotransferase increased † 1	5/195 (2.56%)	6	4/99 (4.04%)	4	2/22 (9.09%)	2	1/10 (10.00%)	3
Bilirubin conjugated increased † 1	0/195 (0.00%)	0	0/99 (0.00%)	0	0/22 (0.00%)	0	1/10 (10.00%)	4
Blood bilirubin increased † 1	1/195 (0.51%)	2	0/99 (0.00%)	0	0/22 (0.00%)	0	1/10 (10.00%)	2
Blood bilirubin unconjugated increased † 1	0/195 (0.00%)	0	0/99 (0.00%)	0	0/22 (0.00%)	0	1/10 (10.00%)	1
Blood creatinine increased † 1	20/195 (10.26%)	29	1/99 (1.01%)	1	0/22 (0.00%)	0	0/10 (0.00%)	0
Haemoglobin decreased † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	1/10 (10.00%)	1
Neutrophil count decreased † 1	18/195 (9.23%)	39	1/99 (1.01%)	2	5/22 (22.73%)	12	1/10 (10.00%)	1
Platelet count decreased † 1	15/195 (7.69%)	31	1/99 (1.01%)	1	4/22 (18.18%)	13	0/10 (0.00%)	0
Blood glucose increased † 1	0/195 (0.00%)	0	0/99 (0.00%)	0	0/22 (0.00%)	0	1/10 (10.00%)	5
White blood cell count decreased † 1	13/195 (6.67%)	40	1/99 (1.01%)	2	5/22 (22.73%)	9	1/10 (10.00%)	2
Metabolism and nutrition disorders
Decreased appetite † 1	44/195 (22.56%)	59	11/99 (11.11%)	11	8/22 (36.36%)	10	2/10 (20.00%)	3
Hyperlipidaemia † 1	0/195 (0.00%)	0	0/99 (0.00%)	0	0/22 (0.00%)	0	1/10 (10.00%)	2
Hypokalaemia † 1	11/195 (5.64%)	15	2/99 (2.02%)	2	1/22 (4.55%)	1	0/10 (0.00%)	0
Hypomagnesaemia † 1	29/195 (14.87%)	54	10/99 (10.10%)	10	0/22 (0.00%)	0	0/10 (0.00%)	0
Musculoskeletal and connective tissue disorders
Pain in extremity † 1	18/195 (9.23%)	23	7/99 (7.07%)	8	0/22 (0.00%)	0	1/10 (10.00%)	1
Periarthritis † 1	0/195 (0.00%)	0	2/99 (2.02%)	2	2/22 (9.09%)	2	0/10 (0.00%)	0
Spinal osteoarthritis † 1	1/195 (0.51%)	1	1/99 (1.01%)	1	0/22 (0.00%)	0	1/10 (10.00%)	1
Arthralgia † 1	31/195 (15.90%)	33	14/99 (14.14%)	14	1/22 (4.55%)	1	0/10 (0.00%)	0
Back pain † 1	32/195 (16.41%)	43	13/99 (13.13%)	15	0/22 (0.00%)	0	0/10 (0.00%)	0
Bone pain † 1	8/195 (4.10%)	8	1/99 (1.01%)	1	0/22 (0.00%)	0	1/10 (10.00%)	1
Coccydynia † 1	0/195 (0.00%)	0	0/99 (0.00%)	0	0/22 (0.00%)	0	1/10 (10.00%)	1
Muscle spasms † 1	19/195 (9.74%)	28	5/99 (5.05%)	5	0/22 (0.00%)	0	0/10 (0.00%)	0
Musculoskeletal chest pain † 1	10/195 (5.13%)	11	3/99 (3.03%)	3	1/22 (4.55%)	1	1/10 (10.00%)	1
Musculoskeletal pain † 1	9/195 (4.62%)	11	7/99 (7.07%)	7	2/22 (9.09%)	2	0/10 (0.00%)	0
Myalgia † 1	18/195 (9.23%)	20	5/99 (5.05%)	8	1/22 (4.55%)	2	1/10 (10.00%)	1
Nervous system disorders
Dizziness † 1	34/195 (17.44%)	43	6/99 (6.06%)	7	4/22 (18.18%)	4	0/10 (0.00%)	0
Dysgeusia † 1	38/195 (19.49%)	46	6/99 (6.06%)	6	1/22 (4.55%)	1	0/10 (0.00%)	0
Headache † 1	50/195 (25.64%)	82	14/99 (14.14%)	15	0/22 (0.00%)	0	0/10 (0.00%)	0
Neuropathy peripheral † 1	11/195 (5.64%)	11	4/99 (4.04%)	4	0/22 (0.00%)	0	0/10 (0.00%)	0
Paraesthesia † 1	12/195 (6.15%)	13	5/99 (5.05%)	5	0/22 (0.00%)	0	0/10 (0.00%)	0
Taste disorder † 1	14/195 (7.18%)	15	1/99 (1.01%)	1	0/22 (0.00%)	0	0/10 (0.00%)	0
Psychiatric disorders
Anxiety † 1	13/195 (6.67%)	16	5/99 (5.05%)	5	1/22 (4.55%)	1	0/10 (0.00%)	0
Depression † 1	13/195 (6.67%)	13	0/99 (0.00%)	0	0/22 (0.00%)	0	0/10 (0.00%)	0
Insomnia † 1	14/195 (7.18%)	20	9/99 (9.09%)	9	2/22 (9.09%)	2	0/10 (0.00%)	0
Reproductive system and breast disorders
Breast pain † 1	0/195 (0.00%)	0	0/99 (0.00%)	0	0/22 (0.00%)	0	1/10 (10.00%)	1
Respiratory, thoracic and mediastinal disorders
Asthma † 1	1/195 (0.51%)	1	0/99 (0.00%)	0	0/22 (0.00%)	0	1/10 (10.00%)	1
Cough † 1	37/195 (18.97%)	54	6/99 (6.06%)	6	0/22 (0.00%)	0	2/10 (20.00%)	2
Dyspnoea † 1	24/195 (12.31%)	33	1/99 (1.01%)	1	1/22 (4.55%)	1	0/10 (0.00%)	0
Oropharyngeal pain † 1	15/195 (7.69%)	19	5/99 (5.05%)	5	1/22 (4.55%)	1	0/10 (0.00%)	0
Productive cough † 1	4/195 (2.05%)	6	0/99 (0.00%)	0	0/22 (0.00%)	0	1/10 (10.00%)	1
Skin and subcutaneous tissue disorders
Alopecia † 1	14/195 (7.18%)	15	6/99 (6.06%)	6	0/22 (0.00%)	0	0/10 (0.00%)	0
Pruritus † 1	14/195 (7.18%)	16	5/99 (5.05%)	6	1/22 (4.55%)	1	0/10 (0.00%)	0
Rash † 1	14/195 (7.18%)	18	5/99 (5.05%)	5	1/22 (4.55%)	1	2/10 (20.00%)	2
1 Term from vocabulary, MedDRA 22.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

The outbreak of the COVID-19 pandemic shortly before the final OS DCO (03 February 2020) was not judged to meaningfully impact the overall quality of the study, including the conduct, data, and interpretation of results.

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: Global Clinical Program Lead
• Organization: AstraZeneca
• Phone: 1-877-240-9479
• EMail: information.center@astrazeneca.com

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

Frenel JS, Kim JW, Aryal N, Asher R, Berton D, Vidal L, Pautier P, Ledermann JA, Penson RT, Oza AM, Korach J, Huzarski T, Pignata S, Colombo N, Park-Simon TW, Tamura K, Sonke GS, Freimund AE, Lee CK, Pujade-Lauraine E. Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial. Ann Oncol. 2022 Oct;33(10):1021-1028. doi: 10.1016/j.annonc.2022.06.011. Epub 2022 Jun 27.

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.

Poveda A, Floquet A, Ledermann JA, Asher R, Penson RT, Oza AM, Korach J, Huzarski T, Pignata S, Friedlander M, Baldoni A, Park-Simon TW, Tamura K, Sonke GS, Lisyanskaya A, Kim JH, Filho EA, Milenkova T, Lowe ES, Rowe P, Vergote I, Pujade-Lauraine E; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):620-631. doi: 10.1016/S1470-2045(21)00073-5. Epub 2021 Mar 18.

Tjokrowidjaja A, Lee CK, Friedlander M, Gebski V, Gladieff L, Ledermann J, Penson R, Oza A, Korach J, Huzarski T, Manso L, Pisano C, Asher R, Lord SJ, Kim SI, Lee JY, Colombo N, Park-Simon TW, Fujiwara K, Sonke G, Vergote I, Kim JW, Pujade-Lauraine E. Concordance between CA-125 and RECIST progression in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer treated in the SOLO2 trial with olaparib as maintenance therapy after response to chemotherapy. Eur J Cancer. 2020 Nov;139:59-67. doi: 10.1016/j.ejca.2020.08.021. Epub 2020 Sep 23.

Friedlander M, Gebski V, Gibbs E, Davies L, Bloomfield R, Hilpert F, Wenzel LB, Eek D, Rodrigues M, Clamp A, Penson RT, Provencher D, Korach J, Huzarski T, Vidal L, Salutari V, Scott C, Nicoletto MO, Tamura K, Espinoza D, Joly F, Pujade-Lauraine E. Health-related quality of life and patient-centred outcomes with olaparib maintenance after chemotherapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT Ov-21): a placebo-controlled, phase 3 randomised trial. Lancet Oncol. 2018 Aug;19(8):1126-1134. doi: 10.1016/S1470-2045(18)30343-7. Epub 2018 Jul 17.

Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2. Epub 2017 Jul 25. Erratum In: Lancet Oncol. 2017 Sep;18(9):e510.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01874353
• Other Study ID Numbers: D0816C00002; 2013-001211-75 ( EudraCT Number )
• First Submitted: June 7, 2013
• First Posted: June 11, 2013
• Results First Submitted: September 15, 2017
• Results First Posted: February 7, 2018
• Last Update Posted: April 1, 2024