Abstract CT038: OlympiAD final overall survival: Olaparib versus chemotherapy treatment of physician's choice (TPC) in patients with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm)
Authors: Robson Mark E. , Im Seock-Ah , Senkus Elżbieta , Xu Binghe , Domchek Susan , Masuda Norikazu , Delaloge Suzette , Li Wei , Tung Nadine , Armstrong Anne , Wu Wenting , Goessl Carsten , Runswick Sarah , Conte Pierfranco 
Published: August 2018

Abstract
Background: A significant progression-free survival benefit was shown in OlympiAD (NCT02000622) for patients (pts) with HER2-negative mBC and a gBRCAm receiving olaparib vs TPC (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.43, 0.80; P&lt;0.001). Interim overall survival (OS) data were reported at primary analysis (46% maturity); prespecified final OS data are now reported.
Methods: OlympiAD was a randomized Phase III trial in pts with HER2-negative mBC and a gBRCAm who had received ≤2 lines of chemotherapy for mBC. Randomization (2:1) to olaparib tablet monotherapy (300 mg bid) or single-agent TPC (capecitabine, vinorelbine or eribulin) was stratified by prior chemotherapy (no/yes), prior platinum (no/yes) and receptor status (ER+ and/or PR+ vs TNBC). Data cut-off was 25 September 2017.
Results: Of 302 randomized pts, 205 received olaparib and 91 received TPC (6 TPC pts declined treatment). At final OS analysis, 192/302 deaths had occurred (64% maturity). HR for OS in the olaparib vs TPC group was 0.90 (95% CI 0.66, 1.23; P=NS; median 19.3 months [mo] vs 17.1 mo). Median follow-up for OS was 18.9 mo for olaparib vs 15.5 mo in the TPC group. More pts in the TPC group received subsequent therapy with PARP inhibitors, cytotoxic chemotherapy, platinum and hormonal treatment than in the olaparib group. Predefined subgroup analyses are shown for the three stratification factors (Table).
SubgroupMedian OS (months)HR95% CINominal P*OlaparibTPCPrior chemotherapy for mBCNo (1L)22.614.70.510.29, 0.900.02Yes (2L/3L)18.817.21.130.79, 1.640.52Prior platinum for BCNo20.319.60.910.64, 1.330.63Yes17.213.30.830.49, 1.450.49Receptor statusER+ and/or PR+21.821.30.860.55, 1.360.51TNBC17.414.90.930.62, 1.430.75*Nominal P-values were calculated using a likelihood ratio test; OS stratification factors were prespecified but not alpha-controlled. 1L, first line; 2L, second line; 3L, third line; BC, breast cancer; ER, estrogen receptor; PR, progesterone receptor; TNBC, triple negative breast cancer CTCAE grade ≥3 adverse events were reported in 38 and 50% of pts receiving olaparib or TPC, respectively, at extended safety analysis. 39 (19%) pts and 15 (7%) pts received olaparib for &gt;18 mo and &gt;24 mo, respectively. Conclusions: At final analysis, median OS was 2.2 mo longer for olaparib monotherapy vs TPC in the overall population (not statistically significant). OlympiAD was not powered to show an OS difference for olaparib vs TPC. Benefit appeared greatest in pts with no prior chemotherapy for mBC (7.9 mo longer median OS in olaparib pts vs TPC). Olaparib safety profile was consistent with primary analysis indicating no relevant cumulative toxicity with extended exposure. Citation Format: Mark E. Robson, Seock-Ah Im, Elżbieta Senkus, Binghe Xu, Susan Domchek, Norikazu Masuda, Suzette Delaloge, Wei Li, Nadine Tung, Anne Armstrong, Wenting Wu, Carsten Goessl, Sarah Runswick, Pierfranco Conte. OlympiAD final overall survival: Olaparib versus chemotherapy treatment of physician's choice (TPC) in patients with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT038.