A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline <i>BRCA1/2</i> Mutations (ABRAZO).

Abstract

To assess talazoparib activity in germline <i>BRCA1/2</i> mutation carriers with advanced breast cancer. ABRAZO (NCT02034916) was a two-cohort, two-stage, phase II study of talazoparib (1 mg/day) in germline <i>BRCA</i> mutation carriers with a response to prior platinum with no progression on or within 8 weeks of the last platinum dose (cohort 1) or ≥3 platinum-free cytotoxic regimens (cohort 2) for advanced breast cancer. Primary endpoint was confirmed objective response rate (ORR) by independent radiological assessment. We enrolled 84 patients (cohort 1, <i>n</i> = 49; cohort 2, <i>n</i> = 35) from May 2014 to February 2016. Median age was 50 (range, 31-75) years. Triple-negative breast cancer (TNBC) incidence was 59% (cohort 1) and 17% (cohort 2). Median number of prior cytotoxic regimens for advanced breast cancer was two and four, respectively. Confirmed ORR was 21% [95% confidence interval (CI), 10-35; cohort 1] and 37% [95% CI, 22-55; cohort 2]. Median duration of response was 5.8 and 3.8 months, respectively. Confirmed ORR was 23% (<i>BRCA1</i>), 33% (<i>BRCA2</i>), 26% (TNBC), and 29% (hormone receptor-positive). The most common all-grade adverse events (AE) included anemia (52%), fatigue (45%), and nausea (42%). Talazoparib-related AEs led to drug discontinuation in 3 (4%) patients. In an exploratory analysis, longer platinum-free interval was associated with higher response rate in cohort 1 (0% ORR with interval <8 weeks; 47% ORR with interval >6 months). Talazoparib exhibited promising antitumor activity in patients with advanced breast cancer and germline <i>BRCA</i> mutation.