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Background: Previously,we reported that maintenance treatment with the oral PARP inhibitor olaparib(400 mg bid)led to a significant PFS improvement vs placebo in patients(pts)with platinum-sensitive relapsed SOC(Ledermann et al NEJM2012).A preplanned subgroup analysis from this randomized,double-blind Phase Ⅱ trial(NCT00753545)suggested that olaparib may lead to a greater PFS,and an OS,benefit in pts with a known germline BRCAm(gBRCAm).Since gBRCA wild-type(gBRCAwt)pts may develop somatic tumor(t)BRCAm,efficacy analyses were performed for all pts with BRCAm.Methods: gBRCAm status was determined retrospectively for all consenting pts(n = 166)using blood samples taken before randomization.tBRCAm status was determined from archival tumor samples of 196 pts.We analyzed PFS/OS by gBRCAm and total BRCAm status.Preliminary data are reported.Results: gBRCA status was known for 218/265 pts(gBRCAm,96; gBRCAwt,122).Including tBRCAm,136 pts had a BRCAm(BRCAwt,116).gBRCAm pts had the greatest PFS benefit with olaparib maintenance vs placebo(median: 11.2 vs 4.1 months [m]; HR,0.17; 95%CI 0.09-0.32; P<0.001)and a significant QoL improvement,as measured with Trial Outcome Index(OR,4.08; 95%CI 1.11-19.85; p = 0.03).The PFS benefit was consistent when tBRCAm pts were included(median: 11.2 vs 4.3 m; HR,0.19; 95%CI 0.11-0.32; p <0.0001).In an interim analysis of OS(58%maturity),a comparison of olaparib vs placebo in the overall population led to a HR of 0.88(95%CI 0.64-1.21)with medians of 29.8 vs 27.8 m,respectively.Although HRs from the gBRCAm and gBRCAwt subgroups were similar(0.85 and 0.84,respectively),13/37 gBRCAm placebo pts received a subsequent PARP inhibitor,confounding the OS data in this subgroup.The analysis of all BRCAm pts was less confounded and resulted in an OS HR of 0.74(95%CI 0.46-1.19; median: 34.9 vs 31.9 m).19 pts have received olaparib for >3 years.Olaparib tolerability was similar in BRCAm pts and the overall population.Conclusions: Olaparib maintenance treatment led to the greatest clinical benefit in pts with a BRCAm.These compelling data warrant confirmation in phase Ⅲ trials.