Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial

摘要: Summary Background In patients with platinum-sensitive recurrent serous ovarian cancer, maintenance monotherapy the PARP inhibitor olaparib significantly improves progression-free survival versus placebo. We assessed effect of on overall in including those BRCA1 and BRCA2 mutations ( BRCA m). Methods this randomised, placebo-controlled, double-blind, phase 2 trial involving 82 sites across 16 countries, cancer who had received two or more courses platinum-based chemotherapy responded to their latest regimen were randomly assigned (1:1) using a computer-generated sequence receive oral (as capsules; 400 mg twice day) matching placebo by an interactive voice response system. Patients stratified ancestry, time progression penultimate platinum, most recent platinum. investigators masked treatment assignment use unique identifiers generated during randomisation. The primary endpoint was survival. updated analysis, we present data for survival, secondary endpoint, from third analysis after than 5 years' follow-up (intention-to-treat population). did described Article at 77% maturity, two-sided α 0·95%. As study not powered assess should be regarded as descriptive p values are nominal. analysed all least one dose safety. This is ongoing registered ClinicalTrials.gov, number NCT00753545. Findings Between Aug 28, 2008, Feb 9, 2010, 265 (n=136) (n=129). 136 deleterious m. cutoff Sept 30, 2015. An advantage seen (hazard ratio [HR] 0·73 [95% CI 0·55–0·96]; nominal p=0·025, which meet required threshold statistical significance [p vs 27·8 months [24·9–33·7] treated placebo), m (HR 0·62 0·41–0·94] p=0·025; 34·9 29·2–54·6] 30·2 [23·1–40·7]). wild-type HR 0·83 (95% 0·55–1·24, p=0·37; 24·5 [19·8–35·0] 26·6 [23·1–32·5] placebo). 11 (15%) 74 years more. Overall, common grade 3 worse adverse events groups fatigue (11 [8%] four [3%] 128) anaemia (eight [6%] [1%]). 30 (22%) group (9%) 128 reported serious events. more, included low-grade nausea (24 [75%] 32 [40%] five), (18 [56%] vomiting (12 [38%] zero), [25%] [20%] five); generally, initially first treatment. Interpretation Despite reaching significance, -mutated receiving appeared have longer supporting benefit. Clinically useful long-term exposure no new safety signals. Taken together, these support both clinical benefit tolerability cancer. Funding AstraZeneca.