Olaparib Treatment in relapsed germline Breast Cancer susceptibility gene (BRCA) Mutated Ovarian Cancer Patients who have progressed at least 6 months after last platinum treatment and have received at least 2 prior platinum treatments - SOLO3

Study identifier:D0816C00010

ClinicalTrials.gov identifier:NCT02282020

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase III, Open Label, Randomised, Controlled, Multi-centre Study to assess the efficacy and safety of Olaparib Monotherapy versus Physician’s Choice Single Agent Chemotherapy in the Treatment of Platinum Sensitive Relapsed Ovarian Cancer in Patients carrying germline BRCA1/2 Mutations.

Medical condition

relapsed ovarian cancer, BRCA mutation, Platinum sensitivity

Phase

Phase 3

Healthy volunteers

Study drug

OLAPARIB, Single agent chemotherapy

Sex

Female

Actual Enrollment

266

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 06 Feb 2015

Primary Completion Date: 10 Oct 2018

Study Completion Date: 19 Jul 2022

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: -
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2022 by AstraZeneca

Collaborators

Myriad Genetics - BRACAnalysis test for FDA Premarket Approval (PMA), Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Inclusion and exclusion criteria

Inclusion Criteria

- Patients must be ≥ 18 years of age
- Patients with histologically diagnosed relapsed high grade serous ovarian cancer (including primary peritoneal and/or fallopian tube cancer) or high grade endometrioid cancer. Patients are eligible to undergo BRCA testing even if they have not yet had recurrence or progression of disease >6 months (>/=183 days) after completion of their last platinum therapy.
- Documented germline mutation in Breast Cancer susceptibility genes: BRCA1 and/or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)
- At least one lesion that can be accurately assessed at baseline by CT/MRI and is suitable for repeated assessment.
- Patients must have received at least 2 prior platinum based lines of chemotherapy - Patients must be partially platinum sensitive or platinum sensitive
- Patients must be suitable to start treatment with single agent chemotherapy based on physician’s choice
- Patients must have normal organ and bone marrow function measured within 28 days of randomisation,
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Patients must have a life expectancy ≥ 16 weeks
- Formalin fixed, paraffin embedded tumour sample from the primary or recurrent cancer must be available for central testing.

Exclusion Criteria

- BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental
- Exposure to any investigational product within 30 days or 5 half lives (whichever is longer) prior to randomisation
- Any previous treatment with a Polyadenosine 5'diphosphoribose polymerisation (PARP) inhibitor, including olaparib.
- Patients who have platinum resistant or refractory disease
- Patients receiving any systemic chemotherapy within 3 weeks prior to first dose of study treatment
- Previous single agent exposure to the selected chemotherapy regimen for randomisation. - Prior malignancy in the last 5 years, unless curatively treated and recurrence free (few exceptions apply).

Location

Research Site

Gent, Belgium, 9000

Location

Research Site

Leuven, Belgium, 3000

Location

Research Site

Toronto, ON, Canada, M5G 1X6

Location

Research Site

Montreal, QC, Canada, H2L 4M1

Location

Research Site

Toronto, ON, Canada, M4N 3M5

Location

Research Site

San Francisco, CA, United States, 94118

Location

Research Site

Albany, NY, United States, 12208

Location

Research Site

Towson, MD, United States, 21204

Arms	Assigned Interventions
Experimental: 1/OLAPARIB olaparib 300mg oral tablets; twice daily	Drug: OLAPARIB 300 mg olaparib tablets taken orally twice daily. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria.
Active Comparator: 2/CHEMOTHERAPY Physician's choice single agent chemotherapy	Drug: Single agent chemotherapy Treatment of relapsed disease with single agent chemotherapy based on physician’s choice of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria

Arms

Assigned Interventions

Experimental: 1/OLAPARIB
olaparib 300mg oral tablets; twice daily

Drug: OLAPARIB
300 mg olaparib tablets taken orally twice daily. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria.

Active Comparator: 2/CHEMOTHERAPY
Physician's choice single agent chemotherapy

Drug: Single agent chemotherapy
Treatment of relapsed disease with single agent chemotherapy based on physician’s choice of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 678 patients were screened (gave informed consent) at 94 centres in 13 countries. Of the 678 patients screened, 266 patients were randomised from 78 sites in 13 countries worldwide. A wash-out period of up to 5 weeks was required for participants who have previously taken potent inhibitors or CYP3A4/5 inducers.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized in a 2:1 ratio between olaparib and single agent chemotherapy. Of the 266 patients randomised, 178 patients were in the olaparib arm and 88 in the chemotherapy arm.

Reporting Groups

	Description
Olaparib 300mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Participant Flow: Overall Study

	Olaparib 300mg BID	Single Agent Chemotherapy
STARTED	178	88
Received Treatment	178	76
COMPLETED	19	0
NOT COMPLETED	159	88
Objective Disease Progression	128	30
Adverse Event	18	15
Withdrawal by Subject	7	10
Miscellaneous	5	19
Severe Non-compliance to Protocol	1	0
Developed Discontinuation Criteria	0	2
Withdrew Consent Prior to Dosing	0	12

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Baseline characteristics are displayed for all participants who started the study. This includes the 12 participants who did not receive treatment in the 'Single Agent Chemotherapy' arm.

Reporting Groups

	Description
Olaparib 300mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Baseline Measures

	Olaparib 300mg BID	Single Agent Chemotherapy	Total
Number of Participants [units: Participants]	178	88	266
Age Continuous [units: Years] Mean ± Standard Deviation	58.5 ± 9.3	60.4 ± 9.9	59.2 ± 9.5
Race/Ethnicity, Customized [units: Participants]
White	148	75	223
Black Or African American	1	1	2
Asian	24	10	34
American Indian Or Alaska Native	4	2	6
Other	1	0	1
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	31	16	47
Not Hispanic or Latino	146	72	218
Unknown or Not Reported	1	0	1
Sex: Female, Male [units: Participants]
Female	178	88	266
Male	0	0	0

Outcome Measures

1. Primary Outcome Measure: Objective Response Rate (ORR) [ Time Frame: RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months) ]

Measure Type	Primary
Measure Name	Objective Response Rate (ORR)
Measure Description	To determine the efficacy of olaparib vs. physician’s choice single agent chemotherapy by assessment of Objective Response Rate (ORR) using blinded independent central review (BICR) Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used by a Blinded Independent Central Review (BICR) to assess participant response to treatment ORR is the number of participants with Complete Response (CR) or Partial Response (PR) in the Measurable Disease Analysis Set (MDAS). Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each. Partial response is declared when there is a decrease in sum of diameters of target lesions ≥ 30%.
Time Frame	RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Measurable Disease Analysis Set (MDAS) includes all participants in the Full Analysis Set (FAS) with measurable disease at baseline (as per RECIST 1.1), determined using Blinded Independent Central Review.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	151	72
Objective Response Rate (ORR) [units: Count of Participants]	109	37

Statistical Analysis 1 for Objective Response Rate (ORR)

Groups^[1]	All groups
Method^[3]	Regression, Logistic
P-Value^[4]	0.002
Odds Ratio (OR)^[5]	2.53
95% Confidence Interval	( 1.40 to 4.58 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Model includes a factor for time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months)
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	An odds ratio >1 favours the olaparib arm

2. Secondary Outcome Measure: Progression Free Survival (PFS) [ Time Frame: RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months) ]

Measure Type	Secondary
Measure Name	Progression Free Survival (PFS)
Measure Description	To determine the efficacy of single agent olaparib vs. physician’s choice single agent chemotherapy by progression free survival (PFS) using BICR assessment according to RECIST 1.1 criteria PFS is defined as the time from randomization until the date of objective radiological disease progression according to RECIST 1.1 or death (by any cause in the absence of disease progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to disease progression (i.e., date of RECIST progression/death or censoring – date of randomization +1).
Time Frame	RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	178	88
Progression Free Survival (PFS) [units: Months] Median (95% Confidence Interval)	13.4 (10.9 to 14.1)	9.2 (7.6 to 11.2)

Statistical Analysis 1 for Progression Free Survival (PFS)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.013
Hazard Ratio (HR)^[5]	0.62
95% Confidence Interval	( 0.43 to 0.91 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Determined using a log-rank test with a factor for time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours the olaparib arm

3. Secondary Outcome Measure: Time from Randomisation to Second Progression (PFS2) [ Time Frame: Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months) ]

Measure Type	Secondary
Measure Name	Time from Randomisation to Second Progression (PFS2)
Measure Description	To determine the efficacy of single agent olaparib vs. physician’s choice single agent chemotherapy by second progression (PFS2). Time from randomization to PFS2 is defined as the time from the date of randomization to the earliest of the progression events subsequent to first progression or death. The date of second progression was recorded by the investigator and defined according to local standard clinical practice, and could involve objective radiological, clinical, cancer antigen-125 (CA-125) progression or death. CA-125 progression was assessed per Gynecological Cancer Intergroup (GCIG) criteria.
Time Frame	Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	178	88
Time from Randomisation to Second Progression (PFS2) [units: Months] Median (95% Confidence Interval)	23.6 (19.2 to 26.0)	19.6 (16.9 to 21.8)

Statistical Analysis 1 for Time from Randomisation to Second Progression (PFS2)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.229
Hazard Ratio (HR)^[5]	0.80
95% Confidence Interval	( 0.56 to 1.15 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Determined using a log-rank test with a factor for time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours the olaparib arm

4. Secondary Outcome Measure: Overall Survival (OS) [ Time Frame: Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months) ]

Measure Type	Secondary
Measure Name	Overall Survival (OS)
Measure Description	To determine the efficacy of single agent olaparib vs. physician’s choice single agent chemotherapy by overall survival (OS). Overall survival is defined as the time from the date of randomisation until death due to any cause.
Time Frame	Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	178	88
Overall Survival (OS) [units: Months] Median (95% Confidence Interval)	34.9 (30.0 to 39.2)	32.9 (23.5 to 43.2)

Statistical Analysis 1 for Overall Survival (OS)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.714
Hazard Ratio (HR)^[5]	1.07
95% Confidence Interval	( 0.76 to 1.49 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Determined using a log-rank test with a factor for time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours the olaparib arm

5. Secondary Outcome Measure: Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death [ Time Frame: RECIST and CA-125 follow-up assessments performed every 8 weeks (±1week), up to 48 weeks, then every 12 weeks (±1week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months) ]

Measure Type	Secondary
Measure Name	Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death
Measure Description	To determine the efficacy of single agent olaparib vs. physician’s choice single agent chemotherapy by time to earliest progression by RECIST 1.1 or CA-125 or death. Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used to assess participant response to treatment. CA-125 progression was assessed per Gynecological Cancer Intergroup (GCIG).
Time Frame	RECIST and CA-125 follow-up assessments performed every 8 weeks (±1week), up to 48 weeks, then every 12 weeks (±1week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	178	88
Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death [units: Months] Median (95% Confidence Interval)	11.1 (9.7 to 13.8)	7.9 (6.9 to 9.4)

Statistical Analysis 1 for Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.005
Hazard Ratio (HR)^[5]	0.59
95% Confidence Interval	( 0.41 to 0.85 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Determined using a log-rank test with a factor for time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	A hazard ratio <1 favours the olaparib arm

6. Secondary Outcome Measure: Time From Randomization To First Subsequent Therapy Or Death (TFST) [ Time Frame: Anti-cancer treatments initiated post discontinuation of study treatment and investigator’s opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months) ]

Measure Type	Secondary
Measure Name	Time From Randomization To First Subsequent Therapy Or Death (TFST)
Measure Description	To determine the efficacy of single agent olaparib vs. physician’s choice single agent chemotherapy by time from randomisation to first subsequent therapy or death (TFST) TFST is defined as the time from the date of randomisation to the earlier of first subsequent chemotherapy start date or death. Anti-cancer treatments include chemotherapy and targeted agents.
Time Frame	Anti-cancer treatments initiated post discontinuation of study treatment and investigator’s opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	178	88
Time From Randomization To First Subsequent Therapy Or Death (TFST) [units: Months] Median (95% Confidence Interval)	15.4 (13.5 to 17.6)	10.9 (9.2 to 14.2)

Statistical Analysis 1 for Time From Randomization To First Subsequent Therapy Or Death (TFST)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	<0.001
Hazard Ratio (HR)^[5]	0.49
95% Confidence Interval	( 0.35 to 0.69 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Model included factors for number of prior chemotherapy regimens received for ovarian cancer (2 or 3 prior lines vs 4 or more lines) and time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours the olaparib arm

7. Secondary Outcome Measure: Time From Randomization To Second Subsequent Therapy Or Death (TSST) [ Time Frame: Anti-cancer treatments initiated post discontinuation of study treatment and investigator’s opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months) ]

Measure Type	Secondary
Measure Name	Time From Randomization To Second Subsequent Therapy Or Death (TSST)
Measure Description	To determine the efficacy of single agent olaparib vs. physician’s choice single agent chemotherapy by time from randomisation to second subsequent therapy or death (TSST) TSST was defined as the time from the date of randomisation to the earlier of second subsequent chemotherapy start date or death. Anti-cancer treatments include chemotherapy and targeted agents.
Time Frame	Anti-cancer treatments initiated post discontinuation of study treatment and investigator’s opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	178	88
Time From Randomization To Second Subsequent Therapy Or Death (TSST) [units: Months] Median (95% Confidence Interval)	25.2 (21.3 to 27.8)	19.9 (18.0 to 24.2)

Statistical Analysis 1 for Time From Randomization To Second Subsequent Therapy Or Death (TSST)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.089
Hazard Ratio (HR)^[5]	0.75
95% Confidence Interval	( 0.53 to 1.05 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Model included factors for number of prior chemotherapy regimens received for ovarian cancer (2 or 3 prior lines vs 4 or more lines) and time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours the olaparib arm

8. Secondary Outcome Measure: Time From Randomization To Study Treatment Discontinuation Or Death (TDT) [ Time Frame: Patients randomised to Olaparib administer their tablets orally at a dose of 300 mg twice daily and continue Olaparib until objective disease progression. Assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months) ]

Measure Type	Secondary
Measure Name	Time From Randomization To Study Treatment Discontinuation Or Death (TDT)
Measure Description	To determine the efficacy of single agent olaparib vs. physician’s choice single agent chemotherapy by time to study treatment discontinuation or death (TDT) TDT was defined as the time from randomization to the earlier of the date of study treatment discontinuation or death.
Time Frame	Patients randomised to Olaparib administer their tablets orally at a dose of 300 mg twice daily and continue Olaparib until objective disease progression. Assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	178	88
Time From Randomization To Study Treatment Discontinuation Or Death (TDT) [units: Months] Median (95% Confidence Interval)	13.1 (10.2 to 14.6)	5.1 (4.7 to 6.5)

Statistical Analysis 1 for Time From Randomization To Study Treatment Discontinuation Or Death (TDT)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	<0.001
Hazard Ratio (HR)^[5]	0.20
95% Confidence Interval	( 0.14 to 0.29 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Model included factors for number of prior chemotherapy regimens received for ovarian cancer (2 or 3 prior lines vs 4 or more lines) and time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours the olaparib arm

9. Secondary Outcome Measure: Duration of Response (DoR) [ Time Frame: RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months) ]

Measure Type	Secondary
Measure Name	Duration of Response (DoR)
Measure Description	To determine the efficacy of single agent olaparib vs. physician’s choice single agent chemotherapy by duration of response (DoR) by BICR using RECIST 1.1 criteria for evaluable patients. Duration of response is the time from the first documentation of complete response (CR) or partial response (PR) until the date of progression or death, or the last evaluable RECIST assessment for participants that do not progress or progress after 2 missed assessments. Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used to assess participant response to treatment.
Time Frame	RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Measurable Disease Analysis Set (MDAS) includes all participants in the Full Analysis Set (FAS) with measurable disease at baseline (as per RECIST 1.1), determined using Blinded Independent Central Review.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	109	37
Duration of Response (DoR) [units: Months] Median (Inter-Quartile Range)	9.4 (5.6 to 25.7)	10.2 (5.5 to 15.3)

No statistical analysis provided for Duration of Response (DoR)

10. Secondary Outcome Measure: Time to Response (TTR) [ Time Frame: RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months) ]

Measure Type	Secondary
Measure Name	Time to Response (TTR)
Measure Description	To determine the efficacy of single agent olaparib vs. physician’s choice single agent chemotherapy by time to response (TTR) by BICR using RECIST 1.1 criteria for evaluable patients. TTR was defined as the time from randomization until the date of first documented response by Blinded independent central review (BICR) assessment.
Time Frame	RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Measurable Disease Analysis Set (MDAS) includes all participants in the Full Analysis Set (FAS) with measurable disease at baseline (as per RECIST 1.1), determined using Blinded Independent Central Review.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	109	37
Time to Response (TTR) [units: Months] Median (Inter-Quartile Range)	2.0 (1.8 to 3.9)	3.5 (1.8 to 3.7)

No statistical analysis provided for Time to Response (TTR)

11. Secondary Outcome Measure: Mean Change From Baseline In Trial Outcome Index (TOI) Score [ Time Frame: Baseline (Day 1) to Week 48 (±1 week). DCO: 10Oct2018 ]

Measure Type	Secondary
Measure Name	Mean Change From Baseline In Trial Outcome Index (TOI) Score
Measure Description	To compare the efficacy of single agent olaparib versus physician’s choice single agent chemotherapy on the Health-related Quality of Life (HRQoL) as measured by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy – Ovarian (FACT-O) The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire Version 4. TOI score ranges from 0 to 100, a higher score indicates a higher HRQoL. A negative change in score from baseline indicated a worsening in symptoms.
Time Frame	Baseline (Day 1) to Week 48 (±1 week). DCO: 10Oct2018
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Selected Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Selected Chemotherapy
Number of Participants Analyzed [units:participants]	167	62
Mean Change From Baseline In Trial Outcome Index (TOI) Score [units: Scores on a scale] Mean (Standard Deviation)	-2.4 (11.1)	-3.6 (9.8)

Statistical Analysis 1 for Mean Change From Baseline In Trial Outcome Index (TOI) Score

Groups^[1]	All groups
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.108
Mean Difference (Final Values)^[5]	2.5
95% Confidence Interval	( -0.5 to 5.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Model includes factors for patient, treatment, visit, treatment by visit interaction, baseline TOI score and baseline TOI score by visit interaction.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

12. Secondary Outcome Measure: Number of Participants Who Show an Improvement in TOI Score [ Time Frame: Baseline (Day 1) to Week 48 (±1 week). DCO: 10Oct2018 ]

Measure Type	Secondary
Measure Name	Number of Participants Who Show an Improvement in TOI Score
Measure Description	To compare the efficacy of single agent olaparib versus physician’s choice single agent chemotherapy on the Health-related Quality of Life (HRQoL) as measured by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy – Ovarian (FACT-O) The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire Version 4. TOI score ranges from 0 to 100, a higher score indicates a higher health-related quality of life (HRQoL). A change in at least 10 points was considered clinically relevant.
Time Frame	Baseline (Day 1) to Week 48 (±1 week). DCO: 10Oct2018
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	168	69
Number of Participants Who Show an Improvement in TOI Score [units: Count of Participants]	25	5

Statistical Analysis 1 for Number of Participants Who Show an Improvement in TOI Score

Groups^[1]	All groups
Method^[3]	Regression, Logistic
P-Value^[4]	0.092
Odds Ratio (OR)^[5]	2.24
95% Confidence Interval	( 0.88 to 6.86 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Estimated from an unadjusted logistic regression model
[5]	Other relevant estimation information:
	An odds ratio > 1 favours the olaparib arm

13. Secondary Outcome Measure: Objective Response Rate (ORR) in Breast Cancer Susceptibility (BRCA) Gene Population by Blinded Independent Central Review (BICR) [ Time Frame: RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months) ]

Measure Type	Secondary
Measure Name	Objective Response Rate (ORR) in Breast Cancer Susceptibility (BRCA) Gene Population by Blinded Independent Central Review (BICR)
Measure Description	BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis). The number of participants with complete or partial response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Partial response is declared when there is a decrease in sum of target disease ≥ 30%. Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each.
Time Frame	RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Measurable Disease Analysis Set (MDAS) includes all participants in the Full Analysis Set (FAS) with measurable disease at baseline (as per RECIST 1.1), determined using Blinded Independent Central Review.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	144	70
Objective Response Rate (ORR) in Breast Cancer Susceptibility (BRCA) Gene Population by Blinded Independent Central Review (BICR) [units: Count of Participants]	103	36

Statistical Analysis 1 for Objective Response Rate (ORR) in Breast Cancer Susceptibility (BRCA) Gene Population by Blinded Independent Central Review (BICR)

Groups^[1]	All groups
Method^[3]	Regression, Logistic
P-Value^[4]	0.004
Odds Ratio (OR)^[5]	2.40
95% Confidence Interval	( 1.32 to 4.39 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Determined using a log-rank test with a factor for time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	An odds ratio > 1 favours the olaparib arm

14. Secondary Outcome Measure: Number of Participants who Experienced Disease Progression or Death in BRCA Gene Population by Blinded Independent Central Review (BICR) [ Time Frame: RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months) ]

Measure Type	Secondary
Measure Name	Number of Participants who Experienced Disease Progression or Death in BRCA Gene Population by Blinded Independent Central Review (BICR)
Measure Description	BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis). Progressive disease was defined as at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame	RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	170	84
Number of Participants who Experienced Disease Progression or Death in BRCA Gene Population by Blinded Independent Central Review (BICR) [units: Count of Participants]	105	48

Statistical Analysis 1 for Number of Participants who Experienced Disease Progression or Death in BRCA Gene Population by Blinded Independent Central Review (BICR)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.014
Hazard Ratio (HR)^[5]	0.62
95% Confidence Interval	( 0.42 to 0.91 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Determined using a log-rank test with a factor for time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours the olaparib arm

15. Secondary Outcome Measure: Number of Participants who Experienced Second Progression or Death (PFS2) in BRCA Gene Population [ Time Frame: Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months) ]

Measure Type	Secondary
Measure Name	Number of Participants who Experienced Second Progression or Death (PFS2) in BRCA Gene Population
Measure Description	BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis).
Time Frame	Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	170	84
Number of Participants who Experienced Second Progression or Death (PFS2) in BRCA Gene Population [units: Count of Participants]	110	48

Statistical Analysis 1 for Number of Participants who Experienced Second Progression or Death (PFS2) in BRCA Gene Population

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.213
Hazard Ratio (HR)^[5]	0.80
95% Confidence Interval	( 0.56 to 1.14 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Determined using a log-rank test with a factor for time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours the olaparib arm

16. Secondary Outcome Measure: Overall Survival (OS) in BRCA Gene Population [ Time Frame: Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months) ]

Measure Type	Secondary
Measure Name	Overall Survival (OS) in BRCA Gene Population
Measure Description	BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis). OS in BRCA gene population was measured by the number of participants who died due to any cause.
Time Frame	Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	170	84
Overall Survival (OS) in BRCA Gene Population [units: Count of Participants]	111	45

Statistical Analysis 1 for Overall Survival (OS) in BRCA Gene Population

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.699
Hazard Ratio (HR)^[5]	1.07
95% Confidence Interval	( 0.76 to 1.51 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Determined using a log-rank test with a factor for time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours the olaparib arm

17. Secondary Outcome Measure: Number of Participants who Discontinued Study Treatment or Died in BRCA Gene Population [ Time Frame: Patients randomised to Olaparib administer their tablets orally at a dose of 300 mg twice daily and continue Olaparib until objective disease progression. Assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months) ]

Measure Type	Secondary
Measure Name	Number of Participants who Discontinued Study Treatment or Died in BRCA Gene Population
Measure Description	BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis).
Time Frame	Patients randomised to Olaparib administer their tablets orally at a dose of 300 mg twice daily and continue Olaparib until objective disease progression. Assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	170	84
Number of Participants who Discontinued Study Treatment or Died in BRCA Gene Population [units: Count of Participants]	151	76

Statistical Analysis 1 for Number of Participants who Discontinued Study Treatment or Died in BRCA Gene Population

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	<0.001
Hazard Ratio (HR)^[5]	0.18
95% Confidence Interval	( 0.12 to 0.27 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Model included factors for number of prior chemotherapy regimens received for ovarian cancer (2 or 3 prior lines vs 4 or more lines) and time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours the olaparib arm

18. Secondary Outcome Measure: Number of Participants who Received Subsequent Chemotherapy or Died in BRCA Gene Population [ Time Frame: Anti-cancer treatments initiated post discontinuation of study treatment and investigator’s opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months) ]

Measure Type	Secondary
Measure Name	Number of Participants who Received Subsequent Chemotherapy or Died in BRCA Gene Population
Measure Description	BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis). Anti-cancer treatments include chemotherapy and targeted agents.
Time Frame	Anti-cancer treatments initiated post discontinuation of study treatment and investigator’s opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Selected Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Selected Chemotherapy
Number of Participants Analyzed [units:participants]	170	84
Number of Participants who Received Subsequent Chemotherapy or Died in BRCA Gene Population [units: Count of Participants]	138	66

Statistical Analysis 1 for Number of Participants who Received Subsequent Chemotherapy or Died in BRCA Gene Population

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	<0.001
Hazard Ratio (HR)^[5]	0.46
95% Confidence Interval	( 0.33 to 0.66 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Model included factors for number of prior chemotherapy regimens received for ovarian cancer (2 or 3 prior lines vs 4 or more lines) and time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours the olaparib arm

19. Secondary Outcome Measure: Number of Participants who Received Second Subsequent Chemotherapy or Died in BRCA Gene Population [ Time Frame: Anti-cancer treatments initiated post discontinuation of study treatment and investigator’s opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months) ]

Measure Type	Secondary
Measure Name	Number of Participants who Received Second Subsequent Chemotherapy or Died in BRCA Gene Population
Measure Description	BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis). Anti-cancer treatments include chemotherapy and targeted agents.
Time Frame	Anti-cancer treatments initiated post discontinuation of study treatment and investigator’s opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	170	84
Number of Participants who Received Second Subsequent Chemotherapy or Died in BRCA Gene Population [units: Count of Participants]	127	56

Statistical Analysis 1 for Number of Participants who Received Second Subsequent Chemotherapy or Died in BRCA Gene Population

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.055
Hazard Ratio (HR)^[5]	0.72
95% Confidence Interval	( 0.51 to 1.01 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Model included factors for number of prior chemotherapy regimens received for ovarian cancer (2 or 3 prior lines vs 4 or more lines) and time to disease progression after the end of last platinum based chemotherapy (6-12 months vs > 12 months).
[5]	Other relevant estimation information:
	A hazard ratio < 1 favours the olaparib arm

20. Secondary Outcome Measure: Geometric Mean Plasma Concentration of Olaparib [ Time Frame: Day 1, 1 hour post-dose and Day 29 pre-dose. DCO: 10Oct2018 ]

Measure Type	Secondary
Measure Name	Geometric Mean Plasma Concentration of Olaparib
Measure Description	Summary of plasma concentrations (ug/mL) of olaparib
Time Frame	Day 1, 1 hour post-dose and Day 29 pre-dose. DCO: 10Oct2018
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The pharmacokinetic (PK) analysis set includes all participants who received an olaparib dose and provided evaluable plasma concentration data.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.

Measured Values

	Olaparib 300 mg BID
Number of Participants Analyzed [units:participants]	66
Geometric Mean Plasma Concentration of Olaparib [units: μg/mL] Geometric Mean (Geometric Coefficient of Variation)
Day 1, 1 hour post-dose	4.76 (112.93%)
Day 29, pre-dose	1.78 (100.54%)

No statistical analysis provided for Geometric Mean Plasma Concentration of Olaparib

21. Secondary Outcome Measure: Number of Participants Who Experience at Least One Adverse Event (AE) [ Time Frame: Safety Follow-up 30 days after last dose of IP, assessed from the date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months) ]

Measure Type	Secondary
Measure Name	Number of Participants Who Experience at Least One Adverse Event (AE)
Measure Description	An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Time Frame	Safety Follow-up 30 days after last dose of IP, assessed from the date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set includes all participants who received at least 1 dose of randomized study treatment, olaparib or chemotherapy.

Reporting Groups

	Description
Olaparib 300 mg BID	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Measured Values

	Olaparib 300 mg BID	Single Agent Chemotherapy
Number of Participants Analyzed [units:participants]	178	76
Number of Participants Who Experience at Least One Adverse Event (AE) [units: Count of Participants]	175	73

No statistical analysis provided for Number of Participants Who Experience at Least One Adverse Event (AE)

Serious Adverse Events

Time Frame	Includes all AEs that had a start date or a worsening (increase in CTCAE grade) after the start of treatment up until the end of the 30 day follow-up period. The 30 day follow-up period will be defined as 30 days following discontinuation of olaparib/chemotherapy treatment. Assessed from randomisation to data cut off. DCO: 16Apr2021
Additional Description	All-Cause Mortality was collected for the Full Analysis Set (FAS). Serious Adverse Events and Other Adverse Events were collected for the Safety Analysis Set (SAS), which includes patients who received at least 1 dose of the randomised study treatment.

Reporting Groups

	Description
Olaparib 300 mg bd	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Serious Adverse Events

Olaparib 300 mg bd

Single Agent Chemotherapy

Total, serious adverse events

# participants affected / at risk

46/178 (25.84%)

14/76 (18.42%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

6/178 (3.37%)

0/76 (0.00%)

# events

Ear and labyrinth disorders

Vertigo¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

0/178 (0.00%)

1/76 (1.32%)

# events

Gastrointestinal disorders

Intestinal obstruction¹,^†

# participants affected / at risk

2/178 (1.12%)

1/76 (1.32%)

# events

Gastrointestinal disorders

Mesenteric vein thrombosis¹,^†

# participants affected / at risk

0/178 (0.00%)

1/76 (1.32%)

# events

Immune system disorders

Anaphylactic reaction¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Infections and infestations

Corneal abscess¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

2/178 (1.12%)

0/76 (0.00%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

2/178 (1.12%)

0/76 (0.00%)

# events

Gastrointestinal disorders

Ileus¹,^†

# participants affected / at risk

2/178 (1.12%)

0/76 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Periarthritis¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Rotator cuff syndrome¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

General disorders and administration site conditions

Chest pain¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

General disorders and administration site conditions

Malaise¹,^†

# participants affected / at risk

0/178 (0.00%)

1/76 (1.32%)

# events

General disorders and administration site conditions

Oedema peripheral¹,^†

# participants affected / at risk

0/178 (0.00%)

1/76 (1.32%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

2/178 (1.12%)

2/76 (2.63%)

# events

Hepatobiliary disorders

Cholecystitis¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Infections and infestations

Device related infection¹,^†

# participants affected / at risk

0/178 (0.00%)

1/76 (1.32%)

# events

Infections and infestations

Herpes zoster¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

2/178 (1.12%)

1/76 (1.32%)

# events

Injury, poisoning and procedural complications

Radius fracture¹,^†

# participants affected / at risk

1/178 (0.56%)

1/76 (1.32%)

# events

Injury, poisoning and procedural complications

Spinal compression fracture¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Investigations

Blood creatinine increased¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Metabolism and nutrition disorders

Electrolyte imbalance¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

0/178 (0.00%)

1/76 (1.32%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastric cancer¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Nervous system disorders

Ischaemic stroke¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

2/178 (1.12%)

0/76 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

3/178 (1.69%)

2/76 (2.63%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

2/178 (1.12%)

0/76 (0.00%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

3/178 (1.69%)

0/76 (0.00%)

# events

Vascular disorders

Embolism¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Gastrointestinal disorders

Anal inflammation¹,^†

# participants affected / at risk

0/178 (0.00%)

1/76 (1.32%)

# events

Gastrointestinal disorders

Ascites¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

2/178 (1.12%)

2/76 (2.63%)

# events

Gastrointestinal disorders

Oesophagitis¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Gastrointestinal disorders

Small intestinal obstruction¹,^†

# participants affected / at risk

2/178 (1.12%)

0/76 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

3/178 (1.69%)

3/76 (3.95%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

2/178 (1.12%)

1/76 (1.32%)

# events

Infections and infestations

Pyelonephritis¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

2/178 (1.12%)

0/76 (0.00%)

# events

Blood and lymphatic system disorders

Pancytopenia¹,^†

# participants affected / at risk

2/178 (1.12%)

0/76 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Cervical spinal stenosis¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Cardiac disorders

Cardiopulmonary failure¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Acute myeloid leukaemia¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer¹,^†

# participants affected / at risk

2/178 (1.12%)

0/76 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung neoplasm malignant¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Myelodysplastic syndrome¹,^†

# participants affected / at risk

2/178 (1.12%)

0/76 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Myeloid leukaemia¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Ear and labyrinth disorders

Tinnitus¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Nervous system disorders

Subarachnoid haemorrhage¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Renal and urinary disorders

Diabetic nephropathy¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Renal and urinary disorders

Renal failure¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

Renal and urinary disorders

Urinary tract obstruction¹,^†

# participants affected / at risk

1/178 (0.56%)

0/76 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 24.0

Other Adverse Events

Time Frame	Includes all AEs that had a start date or a worsening (increase in CTCAE grade) after the start of treatment up until the end of the 30 day follow-up period. The 30 day follow-up period will be defined as 30 days following discontinuation of olaparib/chemotherapy treatment. Assessed from randomisation to data cut off. DCO: 16Apr2021
Additional Description	All-Cause Mortality was collected for the Full Analysis Set (FAS). Serious Adverse Events and Other Adverse Events were collected for the Safety Analysis Set (SAS), which includes patients who received at least 1 dose of the randomised study treatment.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Olaparib 300 mg bd	Participants received olaparib twice daily as a 300 mg tablet.
Single Agent Chemotherapy	Participants received physician’s choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Other Adverse Events

Olaparib 300 mg bd

Single Agent Chemotherapy

Total, other (not including serious) adverse events

# participants affected / at risk

173/178 (97.19%)

73/76 (96.05%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

87/178 (48.88%)

19/76 (25.00%)

# events

163

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

29/178 (16.29%)

22/76 (28.95%)

# events

Gastrointestinal disorders

Abdominal distension¹,^†

# participants affected / at risk

11/178 (6.18%)

1/76 (1.32%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

16/178 (8.99%)

8/76 (10.53%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

5/178 (2.81%)

4/76 (5.26%)

# events

Investigations

Neutrophil count decreased¹,^†

# participants affected / at risk

16/178 (8.99%)

10/76 (13.16%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

17/178 (9.55%)

3/76 (3.95%)

# events

Nervous system disorders

Neuropathy peripheral¹,^†

# participants affected / at risk

5/178 (2.81%)

8/76 (10.53%)

# events

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

9/178 (5.06%)

2/76 (2.63%)

# events

Skin and subcutaneous tissue disorders

Dry skin¹,^†

# participants affected / at risk

0/178 (0.00%)

4/76 (5.26%)

# events

Skin and subcutaneous tissue disorders

Skin hyperpigmentation¹,^†

# participants affected / at risk

1/178 (0.56%)

4/76 (5.26%)

# events

Skin and subcutaneous tissue disorders

Palmar-plantar erythrodysaesthesia syndrome¹,^†

# participants affected / at risk

1/178 (0.56%)

27/76 (35.53%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

5/178 (2.81%)

5/76 (6.58%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

13/178 (7.30%)

9/76 (11.84%)

# events

Skin and subcutaneous tissue disorders

Rash maculo-papular¹,^†

# participants affected / at risk

1/178 (0.56%)

4/76 (5.26%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

41/178 (23.03%)

11/76 (14.47%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

21/178 (11.80%)

4/76 (5.26%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

24/178 (13.48%)

17/76 (22.37%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

52/178 (29.21%)

13/76 (17.11%)

# events

149

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

19/178 (10.67%)

7/76 (9.21%)

# events

Gastrointestinal disorders

Flatulence¹,^†

# participants affected / at risk

1/178 (0.56%)

4/76 (5.26%)

# events

Gastrointestinal disorders

Gastrooesophageal reflux disease¹,^†

# participants affected / at risk

10/178 (5.62%)

2/76 (2.63%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

115/178 (64.61%)

24/76 (31.58%)

# events

240

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

8/178 (4.49%)

14/76 (18.42%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

66/178 (37.08%)

14/76 (18.42%)

# events

165

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

35/178 (19.66%)

12/76 (15.79%)

# events

Blood and lymphatic system disorders

Leukopenia¹,^†

# participants affected / at risk

13/178 (7.30%)

6/76 (7.89%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

66/178 (37.08%)

20/76 (26.32%)

# events

General disorders and administration site conditions

Influenza like illness¹,^†

# participants affected / at risk

7/178 (3.93%)

4/76 (5.26%)

# events

General disorders and administration site conditions

Mucosal inflammation¹,^†

# participants affected / at risk

5/178 (2.81%)

10/76 (13.16%)

# events

General disorders and administration site conditions

Oedema peripheral¹,^†

# participants affected / at risk

16/178 (8.99%)

10/76 (13.16%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

21/178 (11.80%)

8/76 (10.53%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

10/178 (5.62%)

2/76 (2.63%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

21/178 (11.80%)

4/76 (5.26%)

# events

Investigations

Blood creatinine increased¹,^†

# participants affected / at risk

14/178 (7.87%)

1/76 (1.32%)

# events

Investigations

Gamma-glutamyltransferase increased¹,^†

# participants affected / at risk

6/178 (3.37%)

4/76 (5.26%)

# events

Investigations

White blood cell count decreased¹,^†

# participants affected / at risk

18/178 (10.11%)

9/76 (11.84%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

26/178 (14.61%)

9/76 (11.84%)

# events

Metabolism and nutrition disorders

Hypoalbuminaemia¹,^†

# participants affected / at risk

10/178 (5.62%)

4/76 (5.26%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

12/178 (6.74%)

3/76 (3.95%)

# events

Metabolism and nutrition disorders

Hypomagnesaemia¹,^†

# participants affected / at risk

10/178 (5.62%)

1/76 (1.32%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

16/178 (8.99%)

6/76 (7.89%)

# events

Metabolism and nutrition disorders

Hyponatraemia¹,^†

# participants affected / at risk

9/178 (5.06%)

2/76 (2.63%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

18/178 (10.11%)

6/76 (7.89%)

# events

Musculoskeletal and connective tissue disorders

Muscle spasms¹,^†

# participants affected / at risk

12/178 (6.74%)

0/76 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscular weakness¹,^†

# participants affected / at risk

2/178 (1.12%)

4/76 (5.26%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

9/178 (5.06%)

2/76 (2.63%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

10/178 (5.62%)

6/76 (7.89%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

25/178 (14.04%)

6/76 (7.89%)

# events

Nervous system disorders

Dysgeusia¹,^†

# participants affected / at risk

13/178 (7.30%)

6/76 (7.89%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

29/178 (16.29%)

9/76 (11.84%)

# events

Nervous system disorders

Paraesthesia¹,^†

# participants affected / at risk

7/178 (3.93%)

5/76 (6.58%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

4/178 (2.25%)

6/76 (7.89%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

17/178 (9.55%)

5/76 (6.58%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

18/178 (10.11%)

10/76 (13.16%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

22/178 (12.36%)

8/76 (10.53%)

# events

Respiratory, thoracic and mediastinal disorders

Epistaxis¹,^†

# participants affected / at risk

0/178 (0.00%)

5/76 (6.58%)

# events

Skin and subcutaneous tissue disorders

Alopecia¹,^†

# participants affected / at risk

11/178 (6.18%)

12/76 (15.79%)

# events

Skin and subcutaneous tissue disorders

Erythema¹,^†

# participants affected / at risk

2/178 (1.12%)

4/76 (5.26%)

# events

Skin and subcutaneous tissue disorders

Nail discolouration¹,^†

# participants affected / at risk

0/178 (0.00%)

4/76 (5.26%)

# events

Skin and subcutaneous tissue disorders

Nail disorder¹,^†

# participants affected / at risk

1/178 (0.56%)

6/76 (7.89%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 24.0

Certain Agreements

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

There is NOT 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Leader
Organization:	AstraZeneca AB
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

AstraZeneca Cancer Study Locator Service Phone 677 400 4656 Email astrazeneca@emergingmed.com
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Trial Results Summaries
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Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

Elizabeth Lowe

Elizabeth.Lowe@astrazeneca.com

Investigators

Principal Investigator

Richard T Penson

Harvard Medical School

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

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Research Site

Research Site

AstraZeneca Cancer Study Locator Service Phone 677 400 4656 Email astrazeneca@emergingmed.com

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