Kummar 2015

Methods	Open‐label, multicentre, phase II randomised
Participants	75 women (38 women cyclophosphamide, 37 women veliparib + cyclophosphamide) Women with BRCA mutations and recurrent ovarian or primary peritoneal, fallopian tube or high‐grade serous epithelial ovarian cancer regardless of BRCA mutation status All women had measurable disease by RECIST criteria Women aged 18 years or over (median age 58; range 37 to 79 years) Median 4 (range 1 to 9) previous chemotherapy treatment regimens 2 women had received prior treatment with a PARP inhibitor
Interventions	Women were randomised to receive either cyclophosphamide (C) alone or veliparib + cyclophosphamide (V+C) administered orally 4x per day (C 50 mg, V 60 mg) at 21‐day intervals until disease progression. At progression those in the C alone arm were able to cross over to combination treatment
Outcomes	75 women (38 women C, 37 women V+C) Radiological imaging was performed at baseline and every 3 cycles for assessment of response. At interim analysis, 1 complete response was observed in each arm, with a total of 5 partial responses (PR) in the combination arm and 7 PRs in the cyclophosphamide alone arm, so accrual was stopped The study design had an 88% power to detect the difference between a 15% response rate for C alone versus a 35% response rate for V+C; early closure if fewer responses were observed in the combination arm in the first 65 patients enrolled (half of the total projected accrual) These data are different to those published, following limited author response to requests for clarification, since data were inconsistent in the initial meeting abstract Further data published after initial completion of review and review publication delayed to add in. Clarification of data not provided prior to publication, despite requests Data in final publication differ from data in abstract: One complete response was observed in each arm. "PR was seen in six patients in the cyclophosphamide‐only arm [7/36 (19.4%) responses overall; 95% CI: 8.2‐36.0%], three patients in the combination arm [4/34 (11.8%) responses overall; 95% CI: 3.3‐27.5%], with three partial responses (PR) in the combination arm and six PRs in the cyclophosphamide alone arm." 75 enrolled; only 72 had evaluable disease: 1 treatment was discontinued for adverse events; 1 withdrew from the study; and 1 died before the end of the first cycle No improvement in PFS (median 2.3 and 2.1 months for cyclophosphamide alone versus combination treatment; P value = 0.68) Lymphopenia G3 to 4: C = 3/38 (8%) versus V+C = 13/37 (35%) Anaemia G3 to 4: C = 0/38 (0%) versus V+C = 2/37 (5%) Nausea ‐ no G3 to 4 in either arm Vomiting ‐ no G3 to 4 in either arm Abdominal pain ‐ no G3 to 4 in either arm
Notes	No HR for OS or PFS reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Pts were randomised to receive either C alone or V+C". No additional information provided by authors
Allocation concealment (selection bias)	Unclear risk	No additional information provided by authors
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label ‐ not reported that assessors were blinded. No additional information provided by authors
Incomplete outcome data (attrition bias) All outcomes	Low risk	All 75 patients accounted for at end of study
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement
Other bias	High risk	Closed early at interim analysis as fewer responses in combination arm than pre‐specified in power calculation but powered to only detect a 20% difference in response rates. Authors did not provide further data/clarification