Talazoparib Versus Chemotherapy in Patients with HER2-negative Advanced Breast Cancer and a Germline BRCA1/2 Mutation Enrolled in Asian Countries: Exploratory Subgroup Analysis of the Phase III EMBRACA Trial.

Abstract

Abstract Purpose: We evaluated study outcomes in patients enrolled in Asian regions in the phase III EMBRACA trial of talazoparib vs. chemotherapy.

Materials and methods: Patients with human epidermal growth factor receptor 2-negative germline BRCA1/2-mutated advanced breast cancer who received prior chemotherapy were randomized 2:1 to talazoparib 1 mg/day or chemotherapy (physician's choice). Primary endpoint was progression-free survival (PFS) per independent central review in the intent-to-treat (ITT) population. This post-hoc analysis evaluated efficacy/safety endpoints in the ITT population of patients enrolled in Asian regions.

Results: Thirty-three patients were enrolled at Asian sites (talazoparib, n=23; chemotherapy, n=10). Baseline characteristics were generally comparable with the overall EMBRACA population. In Asian patients, median PFS was 9.0 months (95% confidence interval [CI], 3.0 to 15.2) for talazoparib and 7.1 months (95% CI, 1.2 to not reached) for chemotherapy (hazard ratio [HR], 0.74 [95% CI, 0.22 to 2.44]). Objective response rate was numerically higher for talazoparib vs. chemotherapy (62.5% [95% CI, 35.4 to 84.8] vs. 25.0% [95% CI, 3.2 to 65.1]). Median overall survival was 20.7 months (95% CI, 9.4 to 40.1) versus 21.2 months (95% CI, 2.7 to 35.0) (HR, 1.41 [95% CI, 0.49 to 4.05]). In Asian patients, fewer grade 3/4 adverse events (AEs), serious AEs (SAEs), grade 3/4 SAEs, and AEs resulting in dose reduction/discontinuation occurred with talazoparib than chemotherapy; for talazoparib, the frequency of these events was lower in Asian patients versus overall EMBRACA population.

Conclusion: In this subgroup analysis, talazoparib numerically improved efficacy versus chemotherapy and was generally well tolerated in Asian patients, with fewer grade 3/4 treatment-emergent AE (TEAEs), SAEs, and TEAEs leading to dose modification vs. the overall EMBRACA population.

Keywords: Asian; BRCA1/2 mutation; Breast neoplasms; HER2-negative; PARP inhibitor; Phase III; Talazoparib.