Trial Outcomes & Findings for Ph II Study to Evaluate Olaparib With Abiraterone in Treating Metastatic Castration Resistant Prostate Cancer. (NCT NCT01972217)

NCT ID: NCT01972217

Last Updated: 2023-11-14

Results Overview

The efficacy of olaparib when given in combination with abiraterone was assessed by rPFS, defined as the time from randomisation to disease progression using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 (for soft tissue disease) and Prostate Cancer Working Group 2 (PCWG-2) (for bone disease) criteria, or death. Progression using RECIST 1.1 criteria was defined as at least 20% increase from baseline in the sum of diameters of target lesions, progression of existing non-target lesions, or the appearance of at least 1 new lesion. Progression using PCWG-2 criteria was determined if 2 or more new metastatic bone lesions were observed (with a total of at least 4 new lesions since baseline assessment if observed at the 12 week scan, or persistence of or increase in number of lesions if observed after the 12 week scan as determined by a confirmatory scan at least 6 weeks later or at next scheduled visit).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

158 participants

Primary outcome timeframe

From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months.

Results posted on

2023-11-14

Participant Flow

In this 2-part study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were recruited at 41 sites in Europe, Russia and North America. Part A had 2 cohorts for olaparib dose selection when given with approved treatment abiraterone. Part B compared olaparib versus placebo both with abiraterone in post-chemotherapy mCRPC patients.

Patients dosed in open-label Part A could not participate in Part B which was a randomised, double-blind, placebo-controlled comparison of olaparib + abiraterone versus placebo + abiraterone in patients who had received prior chemotherapy containing docetaxel.

Participant milestones

Participant milestones
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone Patients received olaparib 200 milligrams (mg) twice daily (bid) and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part B: Olaparib + Abiraterone Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part B: Placebo + Abiraterone Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part A: Open-label Safety Run-in Period STARTED	3	13	0	0
Part A: Open-label Safety Run-in Period COMPLETED	2	1	0	0
Part A: Open-label Safety Run-in Period NOT COMPLETED	1	12	0	0
Part B Double-blind, Randomised Period STARTED	0	0	71	71
Part B Double-blind, Randomised Period Received Olaparib/Placebo	0	0	71	71
Part B Double-blind, Randomised Period Received Abiraterone	0	0	71	71
Part B Double-blind, Randomised Period COMPLETED	0	0	25	24
Part B Double-blind, Randomised Period NOT COMPLETED	0	0	46	47

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone Patients received olaparib 200 milligrams (mg) twice daily (bid) and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part B: Olaparib + Abiraterone Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part B: Placebo + Abiraterone Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part A: Open-label Safety Run-in Period Withdrawal by Subject	0	1	0	0
Part A: Open-label Safety Run-in Period Condition under investigation worsened	1	9	0	0
Part A: Open-label Safety Run-in Period Adverse Event	0	1	0	0
Part A: Open-label Safety Run-in Period Death	0	1	0	0
Part B Double-blind, Randomised Period Death	0	0	43	44
Part B Double-blind, Randomised Period Reason not recorded	0	0	1	0
Part B Double-blind, Randomised Period Screen failure	0	0	0	1
Part B Double-blind, Randomised Period Lost to Follow-up	0	0	2	1
Part B Double-blind, Randomised Period Withdrawal by Subject	0	0	0	1

Baseline Characteristics

Ph II Study to Evaluate Olaparib With Abiraterone in Treating Metastatic Castration Resistant Prostate Cancer.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=3 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=13 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part B: Olaparib + Abiraterone n=71 Participants Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part B: Placebo + Abiraterone n=71 Participants Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Total n=158 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	3 Participants n=7 Participants	17 Participants n=5 Participants	22 Participants n=4 Participants	42 Participants n=21 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	10 Participants n=7 Participants	54 Participants n=5 Participants	49 Participants n=4 Participants	116 Participants n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	13 Participants n=7 Participants	71 Participants n=5 Participants	71 Participants n=4 Participants	158 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	11 Participants n=5 Participants	5 Participants n=4 Participants	17 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	13 Participants n=7 Participants	58 Participants n=5 Participants	63 Participants n=4 Participants	136 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	13 Participants n=7 Participants	67 Participants n=5 Participants	67 Participants n=4 Participants	150 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants

PRIMARY outcome

Timeframe: Cohort 1 and 2: From baseline in Part A (Day 1 for each cohort) up to 30 days following last dose of study treatment.

Population: The Part A Safety analysis set consisted of all patients who received at least 1 dose of study treatment in Part A. Treatment group comparisons were based on the initial dose of olaparib actually received.

The safety and tolerability of olaparib in combination with abiraterone was assessed during Part A of the study. The percentage of patients experiencing AEs, including information on seriousness, severity, study treatment relationship and those leading to discontinuation for all doses of olaparib and for abiraterone are presented. Severity of AEs was assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events (CTCAE) v4.0. AEs were assigned to a Grade from 1 through 5 as follows: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life-threatening requiring hospitalisation; Grade 4: Life-threatening consequences; Grade 5: Death related to AE. 'c-r' = causally related 'discont' = discontinuation.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=3 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=13 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part A: Percentage of Patients Experiencing Adverse Events (AEs) Any AE c-r to olaparib + abiraterone	66.7 Percentage of patients	46.2 Percentage of patients
Part A: Percentage of Patients Experiencing Adverse Events (AEs) Any AE c-r to olaparib only	33.3 Percentage of patients	7.7 Percentage of patients
Part A: Percentage of Patients Experiencing Adverse Events (AEs) Any AE c-r to abiraterone only	0 Percentage of patients	15.4 Percentage of patients
Part A: Percentage of Patients Experiencing Adverse Events (AEs) Any AE CTCAE Grade 3 or higher	66.7 Percentage of patients	23.1 Percentage of patients
Part A: Percentage of Patients Experiencing Adverse Events (AEs) Any AE CTCAE Grade 3 or higher c-r to olaparib	0 Percentage of patients	7.7 Percentage of patients
Part A: Percentage of Patients Experiencing Adverse Events (AEs) Any AE CTCAE Grade 3 or higher c-r to abiraterone	0 Percentage of patients	7.7 Percentage of patients
Part A: Percentage of Patients Experiencing Adverse Events (AEs) Any AE with outcome = death	0 Percentage of patients	0 Percentage of patients
Part A: Percentage of Patients Experiencing Adverse Events (AEs) Any serious AE (SAE)	66.7 Percentage of patients	23.1 Percentage of patients
Part A: Percentage of Patients Experiencing Adverse Events (AEs) Any SAE c-r to olaparib	0 Percentage of patients	0 Percentage of patients
Part A: Percentage of Patients Experiencing Adverse Events (AEs) Any SAE c-r to abiraterone	0 Percentage of patients	0 Percentage of patients
Part A: Percentage of Patients Experiencing Adverse Events (AEs) Any AE causing discont of olaparib	0 Percentage of patients	7.7 Percentage of patients
Part A: Percentage of Patients Experiencing Adverse Events (AEs) Any AE causing discont of olaparib c-r to olaparib	0 Percentage of patients	0 Percentage of patients
Part A: Percentage of Patients Experiencing Adverse Events (AEs) Any AE causing discont olaparib c-r to abiraterone	0 Percentage of patients	0 Percentage of patients

PRIMARY outcome

Timeframe: From Day 1 for Cohort 1 and from Day 4 for Cohort 2 up to 14 days treatment with olaparib + abiraterone for 3 patients.

DLTs were assessed by a Safety Review Committee (SRC) after a minimum of 3 patients had received at least 14 days of treatment in Part A. A DLT was defined as any toxicity which was not a recognised AE of abiraterone or prednisolone, and was not attributable to the disease or disease-related processes under investigation, which occurred during a minimum period of 14 days treatment and which included: 1. haematological toxicity CTCAE v4.0 Grade 4 or higher present for more than 4 days (except anaemia); 2. non-haematological toxicity CTCAE v4.0 Grade 3 or higher including infection, corrected QT interval prolongation; 3. any other toxicity that was greater than that at baseline, was clinically significant and/or unacceptable, did not respond to supportive care, resulted in a disruption of dosing schedule of 7 days or more, or was judged to be a DLT by the SRC. A DLT excluded alopecia and isolated laboratory changes of any grade without clinical sequelae or clinical significance.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=3 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=13 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part A: Number of Patients With Dose Limiting Toxicities (DLTs)	2 Patients	4 Patients

PRIMARY outcome

Timeframe: From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months.

Population: The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=71 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=71 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part B: Median Radiological Progression-Free Survival (rPFS) Time	13.8 Months Interval 10.8 to 20.4	8.2 Months Interval 5.5 to 9.7

PRIMARY outcome

Timeframe: From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months.

Population: The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received.

The efficacy of olaparib when given in combination with abiraterone was assessed by rPFS, defined as the time from randomisation to disease progression using RECIST version 1.1 (for soft tissue disease) and PCWG-2 (for bone disease) criteria, or death. Progression using RECIST 1.1 criteria was defined as at least 20% increase from baseline in the sum of diameters of target lesions, progression of existing non-target lesions, or the appearance of at least 1 new lesion. Progression using PCWG-2 criteria was determined if 2 or more new metastatic bone lesions were observed (with a total of at least 4 new lesions since baseline assessment if observed at the 12 week scan, or persistence of or increase in number of lesions if observed after the 12 week scan as determined by a confirmatory scan at least 6 weeks later or at next scheduled visit). The percentage of patients with progression events is presented overall and according to RECIST 1.1 and/or PCWG-2 criteria, or death.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=71 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=71 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part B: Percentage of Patients With Progression Events or Death (rPFS)	64.8 Percentage of patients	76.1 Percentage of patients

SECONDARY outcome

Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Population: The PK analysis set consisted of all patients who received at least 1 dose of olaparib per the protocol, for whom there was at least 1 reportable PK concentration and who had no important protocol deviations or AEs that impacted on PK on all PK sampling days. Only patients with data available for analysis at each time point are presented.

Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib Cmax,ss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=7 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=6 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part A Pharmacokinetics (PK): Olaparib Maximum Plasma Concentration at Steady State (Cmax,ss) Olaparib alone	7.781 micrograms per millilitre (mcg/mL) Geometric Coefficient of Variation 25.06	—
Part A Pharmacokinetics (PK): Olaparib Maximum Plasma Concentration at Steady State (Cmax,ss) Olaparib + abiraterone	6.504 micrograms per millilitre (mcg/mL) Geometric Coefficient of Variation 20.90	7.724 micrograms per millilitre (mcg/mL) Geometric Coefficient of Variation 28.05

SECONDARY outcome

Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone Cmax,ss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=7 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=6 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part A PK: Abiraterone Cmax,ss Abiraterone alone	—	145.8 nanograms per millilitre (ng/mL) Geometric Coefficient of Variation 135.5
Part A PK: Abiraterone Cmax,ss Olaparib + abiraterone	130.7 nanograms per millilitre (ng/mL) Geometric Coefficient of Variation 68.87	86.12 nanograms per millilitre (ng/mL) Geometric Coefficient of Variation 48.88

SECONDARY outcome

Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib tmax,ss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=7 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=6 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part A PK Analysis: Olaparib Time to Reach Maximum Plasma Concentration at Steady State (Tmax,ss) Olaparib alone	2.000 Hours (h) Interval 1.0 to 2.17	—
Part A PK Analysis: Olaparib Time to Reach Maximum Plasma Concentration at Steady State (Tmax,ss) Olaparib + abiraterone	2.080 Hours (h) Interval 2.0 to 4.0	2.000 Hours (h) Interval 0.5 to 3.02

SECONDARY outcome

Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone tmax,ss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=7 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=6 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part A PK: Abiraterone Tmax,ss Olaparib + abiraterone	3.000 Hours Interval 1.08 to 3.0	2.500 Hours Interval 2.0 to 3.02
Part A PK: Abiraterone Tmax,ss Abiraterone alone	—	2.525 Hours Interval 1.0 to 3.0

SECONDARY outcome

Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib Cmin,ss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=7 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=6 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part A PK Analysis: Olaparib Minimum Plasma Concentration at Steady State (Cmin,ss) Olaparib alone	1.264 mcg/mL Geometric Coefficient of Variation 46.58	—
Part A PK Analysis: Olaparib Minimum Plasma Concentration at Steady State (Cmin,ss) Olaparib + abiraterone	0.9170 mcg/mL Geometric Coefficient of Variation 31.56	1.279 mcg/mL Geometric Coefficient of Variation 65.36

SECONDARY outcome

Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone Cmin,ss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=7 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=6 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part A PK: Abiraterone Cmin,ss Abiraterone alone	—	8.376 ng/mL Geometric Coefficient of Variation 96.52
Part A PK: Abiraterone Cmin,ss Olaparib + abiraterone	7.983 ng/mL Geometric Coefficient of Variation 163.3	6.358 ng/mL Geometric Coefficient of Variation 50.96

SECONDARY outcome

Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib AUCss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=7 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=6 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part A PK Analysis: Olaparib Area Under the Plasma Concentration-Time Curve at Steady State (AUCss) Olaparib alone	45.27 mcg*h/mL Geometric Coefficient of Variation 31.89	—
Part A PK Analysis: Olaparib Area Under the Plasma Concentration-Time Curve at Steady State (AUCss) Olaparib + abiraterone	40.83 mcg*h/mL Geometric Coefficient of Variation 11.47	49.51 mcg*h/mL Geometric Coefficient of Variation 37.30

SECONDARY outcome

Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone AUCss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=7 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=6 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part A PK: Abiraterone AUCss Abiraterone alone	—	825.5 ng*h/mL Geometric Coefficient of Variation 105.5
Part A PK: Abiraterone AUCss Olaparib + abiraterone	718.9 ng*h/mL Geometric Coefficient of Variation 102.0	524.6 ng*h/mL Geometric Coefficient of Variation 37.65

SECONDARY outcome

Timeframe: From first dose of study treatment following randomisation in Part B up to 30 days following last dose of study treatment (up to approximately 3 years).

Population: Part B safety analysis set consisted of all patients randomised into Part B of the study who received at least 1 dose of olaparib/placebo.

The safety and tolerability of olaparib when given in combination with abiraterone was assessed during Part B of the study. The percentage of patients experiencing AEs, including information on seriousness, severity, study treatment relationship and those leading to discontinuation for all doses of olaparib and for abiraterone are presented. Severity of AEs was assessed using the NCI Common Terminology CTCAE v4.0. AEs were assigned to a Grade from 1 through 5 as follows: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life-threatening requiring hospitalisation; Grade 4: Life-threatening consequences; Grade 5: Death related to AE. 'c-r' = causally related. 'discont' = discontinuation. 'ola/pla' = olaparib/placebo.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=71 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=71 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part B: Percentage of Patients Experiencing AEs Any SAE c-r to ola/pla	9.9 Percentage of patients	1.4 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any AE c-r to ola/pla + abiraterone	45.1 Percentage of patients	12.7 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any AE c-r to ola/pla only	18.3 Percentage of patients	9.9 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any AE c-r to abiraterone only	1.4 Percentage of patients	7.0 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any AE CTCAE Grade 3 or higher	53.5 Percentage of patients	28.2 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any AE CTCAE Grade 3 or higher c-r to ola/pla	23.9 Percentage of patients	5.6 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any AE CTCAE Grade 3 or higher c-r to abiraterone	16.9 Percentage of patients	1.4 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any AE with outcome = death	5.6 Percentage of patients	1.4 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any AE with outcome = death c-r to ola/pla	1.4 Percentage of patients	0 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any AE with outcome = death c-r to abiraterone	0 Percentage of patients	0 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any SAE	35.2 Percentage of patients	19.7 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any SAE c-r to abiraterone	5.6 Percentage of patients	0 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any AE causing discont of ola/pla	29.6 Percentage of patients	9.9 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any AE causing discont of treatment c-r to ola/pla	16.9 Percentage of patients	5.6 Percentage of patients
Part B: Percentage of Patients Experiencing AEs Any AE causing discont treatment c-r abiraterone	8.5 Percentage of patients	1.4 Percentage of patients

SECONDARY outcome

Timeframe: From baseline, then every 4 weeks up to Week 52, and then every 12 weeks.

Population: The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received. Only patients with data available for analysis are presented.

The best percentage change from baseline in PSA levels was determined to assess the anti-tumour activity of olaparib when given in addition to abiraterone, compared with placebo given in addition to abiraterone. The best percentage change was defined as the biggest reduction in PSA level compared with baseline or smallest increase in the absence of a decrease.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=71 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=71 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part B: Median Best Percentage Change From Baseline in Prostate Specific Antigen (PSA) Levels	-54.16 Percentage change in PSA level Interval -100.0 to 533.2	-49.85 Percentage change in PSA level Interval -100.0 to 230.1

SECONDARY outcome

Timeframe: From baseline, then every 4 weeks up to Week 24, and then every 12 weeks.

Population: The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received.

The percentages of patients with single visit responses and with confirmed responses are presented to assess the anti-tumour activity of olaparib when given in addition to abiraterone, compared with placebo given in addition to abiraterone. A single visit response was defined as any post-dose visit PSA level reduced by 50% or more compared with baseline. A confirmed response was defined as a reduction in PSA level of 50% or more on 2 consecutive occasions at least 4 weeks apart compared with baseline. Patients may have had more than 1 single visit response or confirmed response but were counted once.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=71 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=71 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part B: Percentage of Patients With PSA Responses Confirmed response	47.9 Percentage of patients Interval 40.29 to 55.49	42.3 Percentage of patients Interval 34.74 to 49.77
Part B: Percentage of Patients With PSA Responses Single visit response	50.7 Percentage of patients Interval 43.1 to 58.31	47.9 Percentage of patients Interval 40.29 to 55.49

SECONDARY outcome

Timeframe: From baseline, then every 4 weeks up to Week 24, and then every 12 weeks.

Population: The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received. Only patients with data available for analysis are presented.

The median best percentage change from baseline in CTC levels was determined to assess the anti-tumour activity of olaparib when given in combination with abiraterone, compared with placebo given in addition to abiraterone. The best percentage change was defined as the biggest CTC level reduction compared with baseline or smallest increase in the absence of a decrease.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=71 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=71 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part B: Median Best Percentage Change From Baseline in Circulating Tumour Cell (CTC) Level	-1.0 Percentage change in CTC level Interval -478.0 to 613.0	-1.0 Percentage change in CTC level Interval -1279.0 to 414.0

SECONDARY outcome

Timeframe: From baseline, then every 4 weeks up to Week 52, and then every 12 weeks.

Population: The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received. Only patients with data available for analysis are presented. Only patients with measurable disease at baseline are included.

The overall radiological ORR was calculated to assess the anti-tumour activity of olaparib in combination with abiraterone, compared with placebo in combination with abiraterone. The best overall ORR was defined as the percentage of patients with at least 1 visit response of complete response (CR) or partial response (PR) in soft tissue disease assessed by RECIST 1.1 and also bone scan status of non-progressive disease or non-evaluable for their bone scans assessed by PCWG-2. CR: Disappearance of all target lesions. Reduction of pathological lymph nodes to \<10 millimetres. PR: At least a 30% decrease in the sum of diameters of target lesions from baseline. The percentage of patients with a response is presented.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=71 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=71 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part B: Percentage of Patients With at Least One Objective Response (Objective Response Rate [ORR])	27.3 Percentage of patients	31.6 Percentage of patients

SECONDARY outcome

Timeframe: From randomisation until analysis cut-off date (up to approximately 3 years).

Population: The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received.

The TFST and TSST were determined to assess the anti-tumour activity of olaparib when given in combination with abiraterone, compared with placebo given in addition to abiraterone. TFST was defined as the time from randomisation to the earlier of first subsequent anti-cancer therapy start date following study treatment discontinuation, or death. TSST was defined as the time from randomisation to the earlier of the second subsequent anti-cancer therapy start date following study treatment discontinuation, or death.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=71 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=71 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Median Time to First Subsequent Therapy (TFST) and Median Time to Second Subsequent Therapy (TSST) TFST	13.5 Months Interval 11.1 to 17.2	9.7 Months Interval 7.3 to 12.9
Median Time to First Subsequent Therapy (TFST) and Median Time to Second Subsequent Therapy (TSST) TSST	19.6 Months Interval 16.5 to 25.1	18.0 Months Interval 16.9 to 20.6

SECONDARY outcome

Timeframe: From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months.

Population: The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received.

OS was determined to assess the efficacy of olaparib when given in addition to abiraterone, compared with placebo given in addition to abiraterone. OS was performed at the time of the analysis of rPFS, and the median OS, calculated using the Kaplan-Meier technique, is presented.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=71 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=71 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part B: Median Overall Survival (OS)	22.7 Months Interval 17.4 to 29.4	20.9 Months Interval 17.6 to 26.3

SECONDARY outcome

Timeframe: From randomisation until analysis cut-off date (up to approximately 3 years).

Population: The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received.

The efficacy of olaparib when given in combination with abiraterone was assessed by PFS2, defined by local standard clinical practice and included objective radiological progression by RECIST 1.1 (soft tissue), symptomatic progression, rise in PSA level or death in the absence of overall progression.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaparib 200 mg + Abiraterone n=71 Participants Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Part A Cohort 2: Olaparib 300 mg + Abiraterone n=71 Participants If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Part B: Median Time to Second Progression or Death (PFS2)	23.3 Months Interval 17.4 to Insufficient number of patients with events to allow calculation of upper limit for 95% confidence interval.	18.5 Months Interval 16.1 to 23.8

Adverse Events

Part A Cohort 1: Olaparib 200 mg + Abiraterone

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A Cohort 2: Olaparib 300 mg + Abiraterone

Serious events: 3 serious events

Other events: 7 other events

Deaths: 1 deaths

Part B: Olaparib + Abiraterone

Serious events: 25 serious events

Other events: 63 other events

Deaths: 43 deaths

Part B: Placebo + Abiraterone

Serious events: 14 serious events

Other events: 52 other events

Deaths: 45 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

AstraZeneca

Phone: +13028851180

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place