Background: Talazoparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved in the US for HER2-negative germline BRCA1/2-mutated (gBRCA1/2mut) locally advanced/metastatic breast cancer. Approval was based on results from the Phase 3 EMBRACA trial comparing efficacy and safety of talazoparib (1 mg/day) to physician’s choice of therapy ([PCT]; capecitabine, eribulin, gemcitabine, or vinorelbine) in patients with HER2-negative gBRCA1/2mut locally advanced/metastatic breast cancer.
Objectives: The purpose of this analysis was to describe efficacy and safety outcomes of talazoparib vs PCT in US patients included in the pivotal EMBRACA study.
Methods: Clinical findings from US patients enrolled in EMBRACA were analyzed. Patient characteristics, progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), and safety/adverse events (AEs) were among the parameters assessed.
Results: Of 431 randomized patients, 156 patients (36%) were from the US (talazoparib: 99 patients; PCT: 57 patients). Patient characteristics were balanced, although a higher percentage in the talazoparib arm had more poor prognostic features (e.g. triple-negative breast cancer, disease-free interval <12 months, and more disease sites). A total of 53 patients (53.5%) had hormone receptor (HR)+ breast cancer in the talazoparib arm and 37 patients (64.9%) had HR+ breast cancer in the PCT arm. Talazoparib improved PFS (median 9.0 [95% confidence interval (CI), 7.0-12.9] months) vs PCT (median 5.8 [95% CI, 4.2-6.7] months); hazard ratio (HR [95% CI]), 0.5 (0.3-0.7). ORR occurred in 51 patients (63.0%) receiving talazoparib and 11 patients (24.4%) receiving PCT. CBR was 68.7% (95% CI, 58.6-77.6) for talazoparib and 33.3% (95% CI, 21.4-47.1) for PCT; odds ratio (95% CI), 4.7 (2.2-10.6). Median duration of response was 5.0 months and 3.1 months for talazoparib and PCT, respectively. The most common AEs in the talazoparib arm included anemia, neutropenia, thrombocytopenia, fatigue, nausea, alopecia, and headache; hematologic grade 3/4 AEs occurred more often than nonhematologic AEs. Six out of 99 (6.1%) patients in the talazoparib arm and 6/43 (14.0%) patients in the PCT arm discontinued treatment.
Conclusions: In US patients with HER2-negative gBRCA1/2mut locally advanced/metastatic breast cancer, talazoparib demonstrated significant improvements in outcomes vs PCT with a manageable safety profile.
Note: © 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO Annual Meeting. All rights reserved.
Clinical trial identification: NCT01945775
Funding: This study was sponsored by Medivation, which was acquired by Pfizer in September 2016.