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

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ClinicalTrials.gov Identifier: NCT01874353

Recruitment Status : Active, not recruiting

First Posted : June 11, 2013

Results First Posted : February 7, 2018

Last Update Posted : October 14, 2020

Sponsor:

Collaborators:

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Myriad Genetic Laboratories, Inc.

Merck Sharp & Dohme Corp.

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	337

Participant Flow

Recruitment Details	The first patient was screened on 03 September 2013 and the last patient was screened on 21 November 2014. Patients were screened at 119 centres in 16 countries. Of the 602 patients screened, 295 were randomized.
Pre-assignment Details	It was planned that approximately 264 women with BRCA mutated relapsed ovarian cancer patients 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	Placebo Tablets
Arm/Group Description	Taken orally twice daily	Taken orally twice daily
Arm/Group Description	Taken orally twice daily	Taken orally twice daily
Period Title: Overall Study
Started	196	99
Completed	141	62
Not Completed	55	37
Reason Not Completed
Other	2	0
Lost to Follow-up	1	1
Death	45	27
Withdrawal by Subject	7	9

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
Arm/Group Description		Taken orally twice daily	Taken orally twice daily	Total of all reporting groups
Overall Number of Baseline Participants		196	99	295
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	196 participants	99 participants	295 participants
		57.0 (9.20)	56.6 (8.90)	56.9 (9.09)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	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%
Response to previous platinum chemotherapy Measure Type: Number Unit of measure: Participants	Number Analyzed	196 participants	99 participants	295 participants
Complete Response		91	47	138
Partial Response		105	52	157
Time to disease progression in the penultimate platinum chemotherapy Measure Type: Number Unit of measure: Participants	Number Analyzed	196 participants	99 participants	295 participants
>6 - 12 months		79	40	119
>12 months		117	59	176

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 in...
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 up to a maximum of 36 months.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisting of all patients who are randomized


Arm/Group Title	Olaparib 300mg Tablets	Placebo Tablets
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	196	99
Median (95% Confidence Interval) Unit of Measure: Months
	19.1 (16.3 to 25.7)	5.5 (5.2 to 5.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets, Placebo Tablets
	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

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...
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 up to a maximum of 36 months). Analyzed at the time of the primary analysis of PFS and a further analysis of OS will be performed at approximately 60% maturity.

Outcome Measure Data

Analysis Population Description

FAS consisting of all patients who are randomized


Arm/Group Title	Olaparib 300mg Tablets	Placebo Tablets
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	196	99
Median (95% Confidence Interval) Unit of Measure: Months
	NA ^[1] (NA to NA)	NA ^[1] (NA to NA)

[1]

Insufficient OS events to estimate median and 95% confidence interval

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets, Placebo Tablets
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4267
	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	0.80
	Confidence Interval	(2-Sided) 95% 0.50 to 1.31
	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...
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 performed at baseline then every 4 weeks. Radiologic scans performed at baseline then every ~12 weeks up to 72 weeks, then every ~ 24 weeks until objective radiological disease progression. Assessed up to a maximum of 36 months.

Outcome Measure Data

Analysis Population Description

FAS consisting of all patients who are randomized


Arm/Group Title	Olaparib 300mg Tablets	Placebo Tablets
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	196	99
Median (95% Confidence Interval) Unit of Measure: Months
	16.9 (14.6 to 22.3)	4.9 (3.7 to 5.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets, Placebo Tablets
	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

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...
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	Radiologic scans performed at baseline then every 12 weeks for 72 weeks, then every 24 weeks thereafter until first progression. Disease then assessed per local practice every 12 weeks until second progression. Assessed up to a maximum of 36 months.

Outcome Measure Data

Analysis Population Description

FAS consisting of all patients who are randomized


Arm/Group Title	Olaparib 300mg Tablets	Placebo Tablets
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	196	99
Median (95% Confidence Interval) Unit of Measure: Months
	NA ^[1] (24.1 to NA)	18.4 (15.4 to 22.8)

[1]

Insufficient PFS2 events to estimate median and upper confidence limit.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets, Placebo Tablets
	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

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...
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.

Outcome Measure Data

Analysis Population Description

FAS consisting of all patients who are randomized with a baseline and post baseline TOI score available


Arm/Group Title	Olaparib 300mg Tablets	Placebo Tablets
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
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, Placebo Tablets
	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...
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 up to a maximum of 36 months. A further analysis of TFST will be performed at approximately 60% OS maturity.

Outcome Measure Data

Analysis Population Description

FAS consisting of all patients who are randomised


Arm/Group Title	Olaparib 300mg Tablets	Placebo Tablets
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	196	99
Median (95% Confidence Interval) Unit of Measure: Months
	27.9 ^[1] (22.6 to NA)	7.1 (6.3 to 8.3)

[1]

Insufficient TFST events to estimate upper confidence limit.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets, Placebo Tablets
	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	0.28
	Confidence Interval	(2-Sided) 95% 0.21 to 0.38
	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...
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 up to a maximum of 36 months. A further analysis of TSST will be performed at approximately 60% OS maturity.

Outcome Measure Data

Analysis Population Description

FAS consisting of all patients who are randomized


Arm/Group Title	Olaparib 300mg Tablets	Placebo Tablets
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	196	99
Median (95% Confidence Interval) Unit of Measure: Months
	NA ^[1] (NA to NA)	18.2 (15.0 to 20.5)

[1]

Insufficient TSST events for median and 95% confidence interval to be estimated

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets, Placebo Tablets
	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% 0.26 to 0.53
	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...
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 up to a maximum of 36 months. A further analysis of TDT will be performed at approximately 60% OS maturity.

Outcome Measure Data

Analysis Population Description

FAS consisting of all patients who are randomized


Arm/Group Title	Olaparib 300mg Tablets	Placebo Tablets
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
Overall Number of Participants Analyzed	196	99
Median (95% Confidence Interval) Unit of Measure: Months
	19.4 (14.9 to 26.9)	5.6 (5.0 to 7.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 300mg Tablets, Placebo Tablets
	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	0.31
	Confidence Interval	(2-Sided) 95% 0.23 to 0.42
	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 dele...
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.

Outcome Measure Data

Analysis Population Description

FAS consisting of all patients who are randomized and confirmed as Myriad gBRCAm


Arm/Group Title	Olaparib 300mg Tablets	Placebo Tablets
Arm/Group Description:	Taken orally twice daily	Taken orally twice daily
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, Placebo Tablets
	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 m...
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

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


Arm/Group Title	Olaparib 300mg Tablets
Arm/Group Description:	Taken orally twice daily
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	[Not Specified]
Adverse Event Reporting Description	One patient in the olaparib arm was randomised in error and did not receive study treatment.

Arm/Group Title	Olaparib 300mg Tablets		Placebo Tablets
Arm/Group Description	[Not Specified]		[Not Specified]
Arm/Group Description	[Not Specified]		[Not Specified]
All-Cause Mortality
	Olaparib 300mg Tablets		Placebo Tablets
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events Serious Adverse Events
	Olaparib 300mg Tablets		Placebo Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/195 (17.95%)		8/99 (8.08%)
Blood and lymphatic system disorders
Anaemia ^† 1	7/195 (3.59%)	12	0/99 (0.00%)	0
Febrile neutropenia ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Neutropenia ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Total ^† 1	9/195 (4.62%)	14	0/99 (0.00%)	0
Cardiac disorders
Pericarditis ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Total ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Gastrointestinal disorders
Abdominal hernia ^† 1	0/195 (0.00%)	0	1/99 (1.01%)	1
Abdominal pain ^† 1	3/195 (1.54%)	3	0/99 (0.00%)	0
Ascites ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Constipation ^† 1	0/195 (0.00%)	0	2/99 (2.02%)	2
Dysphagia ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Intestinal obstruction ^† 1	3/195 (1.54%)	4	1/99 (1.01%)	1
Nausea ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Small intestinal obstruction ^† 1	0/195 (0.00%)	0	2/99 (2.02%)	3
Vomiting ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Total ^† 1	8/195 (4.10%)	11	5/99 (5.05%)	7
General disorders
Fatigue ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Malaise ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Oedema peripheral ^† 1	1/195 (0.51%)	2	0/99 (0.00%)	0
Pyrexia ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Total ^† 1	4/195 (2.05%)	5	0/99 (0.00%)	0
Hepatobiliary disorders
Cholecystitis ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Total ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Immune system disorders
Anaphylactic reaction ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Hypersensitivity ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Total ^† 1	2/195 (1.03%)	2	0/99 (0.00%)	0
Infections and infestations
Neutropenic sepsis ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Pneumonia ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Urinary tract infection ^† 1	1/195 (0.51%)	1	1/99 (1.01%)	1
Total ^† 1	3/195 (1.54%)	3	1/99 (1.01%)	1
Injury, poisoning and procedural complications
Incisional hernia ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Post procedural fistula ^† 1	0/195 (0.00%)	0	1/99 (1.01%)	1
Total ^† 1	1/195 (0.51%)	1	1/99 (1.01%)	1
Investigations
Amylase increased ^† 1	0/195 (0.00%)	0	1/99 (1.01%)	1
Blood creatine phosphokinase increased ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Blood creatinine increased ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Total ^† 1	2/195 (1.03%)	2	1/99 (1.01%)	1
Metabolism and nutrition disorders
Hypokalaemia ^† 1	0/195 (0.00%)	0	1/99 (1.01%)	1
Total ^† 1	0/195 (0.00%)	0	1/99 (1.01%)	1
Musculoskeletal and connective tissue disorders
Back pain ^† 1	0/195 (0.00%)	0	1/99 (1.01%)	1
Muscular weakness ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Total ^† 1	1/195 (0.51%)	1	1/99 (1.01%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Gastric cancer ^† 1	2/195 (1.03%)	2	0/99 (0.00%)	0
Hepatic neoplasm ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Invasive ductal breast carcinoma ^† 1	0/195 (0.00%)	0	1/99 (1.01%)	1
Myelodysplastic syndrome ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Total ^† 1	5/195 (2.56%)	5	1/99 (1.01%)	1
Renal and urinary disorders
Haematuria ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Total ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Dyspnoea ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Pneumonitis ^† 1	1/195 (0.51%)	1	0/99 (0.00%)	0
Total ^† 1	3/195 (1.54%)	3	0/99 (0.00%)	0
Vascular disorders
Deep vein thrombosis ^† 1	2/195 (1.03%)	2	1/99 (1.01%)	1
Total ^† 1	2/195 (1.03%)	2	1/99 (1.01%)	1
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 19.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Olaparib 300mg Tablets		Placebo Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	192/195 (98.46%)		94/99 (94.95%)
Blood and lymphatic system disorders
Anaemia ^† 1	78/195 (40.00%)	130	7/99 (7.07%)	7
Leukopenia ^† 1	20/195 (10.26%)	27	1/99 (1.01%)	1
Neutropenia ^† 1	22/195 (11.28%)	38	5/99 (5.05%)	11
Thrombocytopenia ^† 1	16/195 (8.21%)	19	3/99 (3.03%)	3
Total ^† 1	92/195 (47.18%)	220	12/99 (12.12%)	22
Cardiac disorders
Total ^† 1	10/195 (5.13%)	11	4/99 (4.04%)	4
Ear and labyrinth disorders
Total ^† 1	18/195 (9.23%)	20	5/99 (5.05%)	5
Eye disorders
Total ^† 1	12/195 (6.15%)	17	4/99 (4.04%)	6
Gastrointestinal disorders
Abdominal distension ^† 1	11/195 (5.64%)	11	7/99 (7.07%)	7
Abdominal pain ^† 1	45/195 (23.08%)	77	31/99 (31.31%)	33
Abdominal pain lower ^† 1	10/195 (5.13%)	10	1/99 (1.01%)	1
Abdominal pain upper ^† 1	21/195 (10.77%)	24	12/99 (12.12%)	13
Constipation ^† 1	40/195 (20.51%)	53	23/99 (23.23%)	29
Diarrhoea ^† 1	64/195 (32.82%)	113	20/99 (20.20%)	28
Dry mouth ^† 1	11/195 (5.64%)	18	4/99 (4.04%)	4
Dyspepsia ^† 1	22/195 (11.28%)	33	8/99 (8.08%)	8
Flatulence ^† 1	10/195 (5.13%)	11	1/99 (1.01%)	1
Gastrooesophageal reflux disease ^† 1	13/195 (6.67%)	13	3/99 (3.03%)	3
Nausea ^† 1	148/195 (75.90%)	265	33/99 (33.33%)	44
Stomatitis ^† 1	20/195 (10.26%)	29	6/99 (6.06%)	7
Total ^† 1	176/195 (90.26%)	891	75/99 (75.76%)	236
Vomiting ^† 1	72/195 (36.92%)	131	19/99 (19.19%)	25
General disorders
Asthenia ^† 1	61/195 (31.28%)	99	27/99 (27.27%)	29
Fatigue ^† 1	74/195 (37.95%)	89	15/99 (15.15%)	22
Influenza like illness ^† 1	12/195 (6.15%)	12	1/99 (1.01%)	1
Mucosal inflammation ^† 1	10/195 (5.13%)	13	3/99 (3.03%)	4
Oedema peripheral ^† 1	15/195 (7.69%)	18	6/99 (6.06%)	7
Pyrexia ^† 1	26/195 (13.33%)	32	6/99 (6.06%)	9
Total ^† 1	152/195 (77.95%)	301	48/99 (48.48%)	77
Infections and infestations
Cystitis ^† 1	13/195 (6.67%)	23	0/99 (0.00%)	0
Influenza ^† 1	13/195 (6.67%)	13	6/99 (6.06%)	6
Nasopharyngitis ^† 1	21/195 (10.77%)	35	11/99 (11.11%)	12
Oral herpes ^† 1	11/195 (5.64%)	14	3/99 (3.03%)	4
Total ^† 1	106/195 (54.36%)	235	39/99 (39.39%)	78
Upper respiratory tract infection ^† 1	14/195 (7.18%)	16	5/99 (5.05%)	9
Urinary tract infection ^† 1	17/195 (8.72%)	22	9/99 (9.09%)	11
Injury, poisoning and procedural complications
Total ^† 1	30/195 (15.38%)	43	10/99 (10.10%)	12
Investigations
Alanine aminotransferase increased ^† 1	10/195 (5.13%)	13	4/99 (4.04%)	4
Blood creatinine increased ^† 1	20/195 (10.26%)	29	1/99 (1.01%)	1
Neutrophil count decreased ^† 1	14/195 (7.18%)	29	1/99 (1.01%)	2
Platelet count decreased ^† 1	12/195 (6.15%)	25	0/99 (0.00%)	0
Total ^† 1	56/195 (28.72%)	178	14/99 (14.14%)	33
White blood cell count decreased ^† 1	11/195 (5.64%)	32	1/99 (1.01%)	2
Metabolism and nutrition disorders
Decreased appetite ^† 1	43/195 (22.05%)	53	11/99 (11.11%)	11
Hypomagnesaemia ^† 1	28/195 (14.36%)	51	10/99 (10.10%)	10
Total ^† 1	88/195 (45.13%)	171	26/99 (26.26%)	41
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	29/195 (14.87%)	31	15/99 (15.15%)	15
Back pain ^† 1	23/195 (11.79%)	28	12/99 (12.12%)	14
Muscle spasms ^† 1	19/195 (9.74%)	25	5/99 (5.05%)	5
Musculoskeletal pain ^† 1	7/195 (3.59%)	9	6/99 (6.06%)	6
Myalgia ^† 1	17/195 (8.72%)	19	5/99 (5.05%)	8
Pain in extremity ^† 1	17/195 (8.72%)	23	7/99 (7.07%)	8
Total ^† 1	89/195 (45.64%)	182	46/99 (46.46%)	78
Nervous system disorders
Dizziness ^† 1	26/195 (13.33%)	33	5/99 (5.05%)	6
Dysgeusia ^† 1	52/195 (26.67%)	60	7/99 (7.07%)	7
Headache ^† 1	49/195 (25.13%)	79	13/99 (13.13%)	14
Neuropathy peripheral ^† 1	12/195 (6.15%)	12	4/99 (4.04%)	5
Paraesthesia ^† 1	10/195 (5.13%)	11	5/99 (5.05%)	5
Total ^† 1	111/195 (56.92%)	238	32/99 (32.32%)	49
Psychiatric disorders
Anxiety ^† 1	12/195 (6.15%)	13	5/99 (5.05%)	5
Insomnia ^† 1	11/195 (5.64%)	14	9/99 (9.09%)	9
Total ^† 1	37/195 (18.97%)	49	14/99 (14.14%)	18
Renal and urinary disorders
Total ^† 1	18/195 (9.23%)	31	11/99 (11.11%)	12
Reproductive system and breast disorders
Total ^† 1	16/195 (8.21%)	22	5/99 (5.05%)	7
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	32/195 (16.41%)	42	5/99 (5.05%)	5
Dyspnoea ^† 1	22/195 (11.28%)	29	1/99 (1.01%)	1
Oropharyngeal pain ^† 1	14/195 (7.18%)	17	5/99 (5.05%)	5
Total ^† 1	72/195 (36.92%)	131	14/99 (14.14%)	17
Skin and subcutaneous tissue disorders
Total ^† 1	58/195 (29.74%)	99	26/99 (26.26%)	32
Alopecia ^† 1	11/195 (5.64%)	11	6/99 (6.06%)	6
Pruritus ^† 1	13/195 (6.67%)	15	4/99 (4.04%)	4
Rash ^† 1	12/195 (6.15%)	16	5/99 (5.05%)	5
Vascular disorders
Total ^† 1	20/195 (10.26%)	23	7/99 (7.07%)	7
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 19.0

Limitations and Caveats

The OS data were immature but there was no indication of an OS detriment, with the HR numerically favouring olaparib. Another analysis of OS will be performed at approximately 60% maturity. Analyses of TFST, TSST and TDT will also be performed.

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

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Name/Title:	Elizabeth Lowe
Organization:	AstraZeneca
EMail:	ClinicalTrialTransparency@astrazeneca.com

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

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.

Layout table for additonal information

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01874353
Other Study ID Numbers:	D0816C00002
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:	October 14, 2020

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