Abstract P5-21-13: Olaparib monotherapy versus chemotherapy for patients with HER2-negative metastatic breast cancer and a germline <i>BRCA</i> mutation: Asian subgroup analysis from the phase III OlympiAD trial
Authors: S-A Im, B Xu, W Li, M Robson, Q Ouyang, D-C Yeh, H Iwata, Y-H Park, JH Sohn, L-M Tseng, C Goessl, W Wu, S Runswick, N Masuda
Journal: Cancer Research (2018)

Abstract Background In the Phase III OlympiAD trial (NCT02000622, D0819C00003), olaparib (Lynparza™) showed a significant progression-free survival (PFS) improvement compared with chemotherapy treatment of physician's choice (TPC) in patients (pts) with metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm) (Robson et al. NEJM 2017). Here, we present data from a subgroup analysis of Asian pts. It is not yet known whether Asian pts, in comparison with the global patient population, may experience instances of differential toxicity with olaparib therapy. Methods OlympiAD, an open-label, multicenter, Phase III trial, randomized (2:1) pts with HER2-negative mBC and a gBRCAm to olaparib tablets (300 mg twice daily) or single-agent TPC (21-day cycles of capecitabine, eribulin or vinorelbine). Pts must have received ≤2 lines of chemotherapy for mBC and prior anthracycline and taxane in the adjuvant, neo-adjuvant or metastatic setting. Primary endpoint was PFS by blinded independent central review (BICR). Region (Asia, Europe, North America, South America) was a pre-defined subgroup for PFS. Results The Asian subgroup analysis included pts randomized at centers in China, Japan, Korea and Taiwan. Of 87 Asian pts randomized (median age 46 years), 86 received study treatment (n=59, olaparib; n=27, TPC). In the olaparib group, 29/59 (49%) had estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+) tumors, and 30/59 (51%) had triple negative breast cancer (TNBC). In the TPC group, 13/28 (46%) had ER+/PR+ tumors and 15/28 (54%) had TNBC. The primary endpoint, PFS by BICR, favored olaparib with a hazard ratio (HR) of 0.53 (95% confidence interval [CI] 0.29–0.97; median 5.7 vs 4.2 months; 77% maturity), and was supported by investigator-assessed PFS (HR 0.29, 95% CI 0.16–0.55). In the overall OlympiAD study population (N=302), the PFS by BICR favored olaparib with a HR of 0.58 (95% CI 0.43–0.80; P=0.0009). Within the Asian subgroup, objective response rate (ORR) (RECIST) was 64% for olaparib versus 38% for the TPC group. Time to second progression, PFS2, was longer for pts receiving olaparib versus TPC (HR 0.43, 95% CI 0.22–0.84; 57% maturity). Grade ≥3 adverse events (AEs) occurred in 46% and 59% of pts receiving olaparib and TPC, respectively. The most common grade ≥3 AE was anemia (olaparib, 20%; TPC, 15%). In both treatment groups, 7% of pts discontinued study treatment due to AEs (n=4, olaparib; n=2, TPC). The tolerability profile of olaparib between the subgroup of Asian pts and the overall OlympiAD population will be examined in our data presentation. Conclusion Olaparib demonstrated an efficacy benefit compared with TPC in pts with HER2-negative mBC and a gBRCAm in this subgroup analysis of Asian pts from the Phase III OlympiAD trial. Discontinuation rates due to toxicity were low, highlighting that olaparib was generally well-tolerated. The efficacy of olaparib within the subgroup of Asian pts was consistent with that shown for the full OlympiAD dataset; consistent hazard ratios were shown in favor of olaparib using the primary endpoint of PFS by BICR, and for the key secondary endpoints of PFS by investigator assessment, PFS2, and ORR. Citation Format: Im S-A, Xu B, Li W, Robson M, Ouyang Q, Yeh D-C, Iwata H, Park Y-H, Sohn JH, Tseng L-M, Goessl C, Wu W, Runswick S, Masuda N. Olaparib monotherapy versus chemotherapy for patients with HER2-negative metastatic breast cancer and a germline BRCA mutation: Asian subgroup analysis from the phase III OlympiAD trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-13.