Seock‐Ah Im

Olaparib efficacy in patients with germline BRCA ‐mutated, HER2 ‐negative metastatic breast cancer: Subgroup analyses from the phase III OlympiAD trial

Abstract In the primary analysis of the phase III OlympiAD trial, olaparib significantly prolonged progression‐free survival (PFS) vs chemotherapy treatment of physician's choice (TPC) in patients with germline BRCA‐mutated (gBRCAm), HER2‐negative metastatic breast cancer (mBC). We report subgroup analyses for the final analysis at a median OS follow‐up of 18.9 months (olaparib) and 15.5 months (TPC). Patients (N = 302) with gBRCAm, HER2‐negative mBC and ≤2 previous lines of chemotherapy for mBC were randomized 2:1 to open‐label olaparib (300 mg twice daily) or TPC. All subgroup analyses were prespecified except site of metastases. Investigator‐assessed median PFS was 8.0 months (95% confidence interval [CI] 5.8‐8.4; 176/205 events) for olaparib and 3.8 months (95% CI 2.8‐4.2; 83/97 events) for TPC (hazard ratio 0.51, 95% CI 0.39‐0.66). In subgroup analyses, median PFS hazard ratios (95% CI) favored olaparib: hormone receptor status (triple‐negative: 0.47, 0.32‐0.69; hormone receptor‐positive: 0.52, 0.36‐0.75); gBRCAm ( BRCA1 : 0.49, 0.35‐0.71; BRCA2 : 0.49, 0.33‐0.74); site of metastases (visceral/CNS: 0.53, 0.40‐0.71; non‐visceral: 0.45, 0.23‐0.98); prior chemotherapy for mBC (yes: 0.51, 0.38‐0.70; no: 0.49, 0.30‐0.82); prior platinum‐based chemotherapy for BC (yes: 0.49, 0.30‐0.83; no: 0.50, 0.37‐0.69); progressive disease at randomization (yes: 0.48, 0.35‐0.65; no: 0.61, 0.36‐1.07). Investigator‐assessed objective response rates were higher across all subgroups with olaparib (35‐68%) vs TPC (5‐40%). Global health status/health‐related quality of life increased in all subgroups with olaparib vs decreased/no change with TPC. These data confirm the consistency of olaparib benefit across patient subgroups in OlympiAD.

Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study

Abstract Purpose: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts). Patients and Methods: In this open-label, multicenter study, PARP inhibitor-naïve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab. Primary endpoints were objective response rate (ORR; gBRCAm expansion doublet cohort), disease control rate (DCR) at 24 weeks (non-gBRCAm cohorts), and safety (all cohorts). Results: The full analysis and safety analysis sets comprised 51, 32, and 31 patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively. ORR was 92.2% [95% confidence interval (CI), 81.1–97.8] in the gBRCAm expansion doublet cohort (primary endpoint); DCR at 24 weeks was 28.1% (90% CI, 15.5–43.9) in the non-gBRCAm doublet cohort (primary endpoint) and 74.2% (90% CI, 58.2–86.5) in the non-gBRCAm triplet cohort (primary endpoint). Grade ≥ 3 adverse events were reported in 47.1%, 65.6%, and 61.3% of patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively, most commonly anemia. Conclusions: Olaparib plus durvalumab continued to show notable clinical activity in women with gBRCAm PSROC. Olaparib plus durvalumab with bevacizumab demonstrated encouraging clinical activity in women with non-gBRCAm PSROC. No new safety signals were identified.