Oza 2015

Methods	Open‐label, randomised, phase II, multicentre study Randomisation (1:1) stratified by number of platinum treatments and platinum‐free interval
Participants	162 women with platinum‐sensitive recurrent high‐grade serous epithelial ovarian cancer Baseline characteristics well balanced between groups. However, 6 randomised to placebo arm withdrew before starting treatment compared to 0 in the OLA group Median age 59.0 (range 27 to 78) (Arm A) 62 (Arm B) (range 31 to 79)
Interventions	Arm A ‐ OLA orally (200 mg bd days 1 to 10 of a 21‐day cycle) in combination with paclitaxel (P) intravenous (IV) (175 mg/m2 day 1 of a 21‐day cycle) and carboplatin (C) IV (AUC4 day 1 of a 21‐day cycle) for at least 4 cycles. Followed by OLA monotherapy maintenance (400 mg bd continuous dosing) Arm B ‐ Paclitaxel (P) IV (175 mg/m2 day 1 of a 21‐day cycle) and carboplatin (C) IV (AUC6 day 1 of a 21‐day cycle) for 6 cycles. Followed by a post‐completion phase in which no study treatment was administered
Outcomes	Primary outcome: progression‐free survival (PFS) by central review (RECIST 1.1) Secondary outcomes: overall survival (OS); objective response rate (ORR); safety 162 women randomised (n = 81 per arm): 156 received treatment (Arm A, n = 81; Arm B, n = 75) and 121 began the maintenance/no further therapy phase (Arm A, n = 66; Arm B, n = 55) Survival and response outcomes OLA + P/C (AUC4) followed by maintenance OLA showed improvement in PFS versus P/C (AUC6) alone (HR 0.51, 95% CI 0.34 to 0.77; P value = 0.0012; median PFS = 12.2 months (95% CI 9.7 to 15.0) versus 9.6 months (95% CI 9.1 to 9.7) OS data (HR 1.17, 95% CI 0.79 to 1.73; P value = 0.4379; median 33.8 versus 37.6 months; 54/81 versus 47/81 deaths in arms A and B respectively; total events = 62%) ORR was similar for Arm A and Arm B (64% versus 58%) Toxicity data (during chemo +/‐ OLA phase) Nausea (G3 to 4): 1/81 (1.2%) (Arm A) and 1/75 (1.3%) (Arm B) Fatigue (G3 to 4): 6/81 (7.4%) (arm A versus 3/75 (4.0%) (Arm B) Abdominal pain: Grade 3 to 4: 0/81 (0%) versus 2/75 (2.67%) (Arm B) Vomiting: Grade 3 to 4: 1/81 (1.23%) versus 0/75 (0%) (Arm B) Anaemia: Grade 3 to 4: 7/82 (8.6%) versus 5/75 (6.7%) Neutropenia: Grade 3 to 4: 35/81 (43.2%) (Arm A) versus 26/75 (34.7%) (Arm B) Toxicity data (during maintenance phase) Nausea (G3 to 4): 1/66 (1.2%) (Arm A) and 0/55 (0%) (Arm B) Fatigue (G3 to 4): 0/66 (0%) (arm A versus 0/55 (0%) (Arm B) Abdominal pain: Grade 3 to 4: 0/66 (0%) versus 0/55 (0%) (Arm B) Vomiting: Grade 3 to 4: 0/66 (1.23%) versus 0/55 (0%) (Arm B) Anaemia: Grade 3 to 4: 5/66 (7.6%) versus 1/55 (1.8%) Neutropenia: Grade 3 to 4: 3/66 (4.5%) (Arm A) versus 0/55 (0%) (Arm B)
Notes	We contacted authors for additional information and they provided us with the in‐press manuscript
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Patient randomisation was stratified (using an interactive voice response [IVR]system) based on:1) number of prior platinum‐containing treatment lines received(1 or >1) and 2) time to disease progression following completion of the previous platinum‐containing therapy(>6 to <=12 months or >12 months)."
Allocation concealment (selection bias)	Low risk	See above
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors for central RECIST review were blinded to treatment groups
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	All patients accounted for from randomisation, although 6 patients in control group withdrew before starting treatment
Selective reporting (reporting bias)	Low risk	Outcomes pre‐specified on clinical trial registry website
Other bias	Unclear risk	Industry‐sponsored by AstraZeneca with several authors disclosing financial conflict of interest

bd: twice a day CI: confidence interval CT: computerised tomography GCIG: Gynaecologic Cancer Intergroup HR: hazard ratio IV: intravenous OLA: olaparib OR: odds ratio ORR: objective response rate OS: overall survival PFS: progression‐free survival PLD: pegylated liposomal doxorubicin PS: performance status pts: patients RECIST: Response Evaluation Criteria in Solid Tumours