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

Abstract

AbstractIn 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.