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

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.

Fig. 1

Patient disposition: Asian and EMBRACA ITT populations. From The New England Journal of Medicine, Litton JK et al, Talazoparib in patients with advanced breast cancer and a germline BRCA mutation, 379:753–63 [8]. Copyright © (2020) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. AE, adverse event; ITT, intent-to-treat; PD, progressive disease. ^a)Including patients who died, withdrew consent or were lost to follow-up, ^b)Preferred terms included anemia, neutropenia, thrombocytopenia, vomiting, fatigue, general physical health deterioration, mucosal inflammation, edema peripheral, accidental overdose, glioblastoma multiforme, metastases to meninges, cerebral hemorrhage, headache, transient ischemic attack, dyspnea, obstructive airways disorder, rash, and rash generalized.

Fig. 2

PFS by blinded central review (A, B) and investigator assessment (C, D) in the ITT populations^a). ^a)From The New England Journal of Medicine, Litton JK et al, Talazoparib in patients with advanced breast cancer and a germline BRCA mutation, 379:753–63 [8]. Copyright © (2020) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. CI, confidence interval; HR, hazard ratio; ITT, intent-to-treat; NR, not reached; PCT, physician’s choice of treatment.