Kaye 2012.

Methods	Phase II open‐label multicentre RCT; 1:1:1 ratio (ID: NCT00628251)
Participants	97 women with ROC within 12 months of receiving platinum‐based chemotherapy with confirmed BRCA1/2 germline mutations; one or more measurable lesion; ECOG PS 0‐2; estimated life expectancy ≥ 16 weeks; adequate bone marrow, hepatic and renal function. Excluded if previous PARP inhibitors or anthracyclines; brain metastases; other malignant disease; persistent toxic effects of treatment; LVEF < 50%
Interventions	Arm 1: OLA 200 mg bd continuously (32 women) Arm 2: OLA 400 mg bd continuously (32 women) Arm 3: PLD 50 mg/m² IVI q4wk (33 women)
Outcomes	Primary: PFS (RECIST‐assessed) Secondary: ORR, duration of treatment response, tumour size, OS, SAE, QoL (FACT‐O)
Notes	PARP nuclear enzymes facilitate DNA repair. Olaparib is a PARP inhibitor selective for homologous‐recombination‐deficient cells, such as those with BRCA1/2 deficiency. The primary outcome was reported for the olaparib arms combined and individually, versus the PLD arm. We used the results from the OLA 400 mg arm versus PLD. Median time to progression was 38 weeks versus 30 weeks in favour of OLA. Median time to death was not calculable for the OLA group and was 76 weeks for the PLD group (unpublished data). Corticosteroids and serotonin antagonists were given to 22/33 (67%) and 14/33 (42%) of the women in the PLD group respectively versus 12.5 % and 12.5% of the OLA group respectively, but it was not possible to determine whether they were given as premedication or at another time (unpublished information).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated, block randomisation, stratified according to BRCA status and platinum sensitivity (≤ 6 months and > 6 months).
Allocation concealment (selection bias)	Low risk	Allocation via an Interactive Voice Response System
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	'Centrally reviewed tumour assessments' were used for analyses; investigator‐assessed primary outcome; assessor blinding/independence not described.
Incomplete outcome data (attrition bias) All outcomes	Low risk	In the PLD arm, 5/33 discontinued treatment for unknown reasons versus 1/64 in the olaparib arm. Otherwise, attrition rates seem low.
Selective reporting (reporting bias)	Low risk	All expected outcomes reported. Results are not reported for platinum‐sensitive subgroups; these data were requested from the lead investigator on the 6/12/12.
Other bias	Low risk	Baseline characteristics were similar except that more women in Arm 2 had received > 2 prior chemotherapy regimens.