A Phase II Study of Talazoparib After Platinum or Cytotoxic Nonplatinum Regimens in Patients With Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO). Clinical cancer research : an official journal of the American Association for Cancer Research Turner, N. C., Telli, M. L., Rugo, H. S., Mailliez, A., Ettl, J., Grischke, E. M., Mina, L. A., Balmaña, J., Fasching, P. A., Hurvitz, S. A., Wardley, A. M., Chappey, C., Hannah, A. L., Robson, M. E. 2018

Abstract

To assess talazoparib activity in germline BRCA1/2 mutation carriers with advanced breast cancer (aBC).ABRAZO (NCT02034916) was a two-cohort, two-stage, phase II study of talazoparib (1 mg/day) in germline BRCA 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 aBC. Primary endpoint was confirmed objective response rate (ORR) by independent radiological assessment.We enrolled 84 patients (cohort 1, n = 49; cohort 2, n = 35) from May 2014 to February 2016. Median age was 50 (range, 31-75) years. Triple-negative breast cancer incidence was 59% (cohort 1) and 17% (cohort 2). Median number of prior cytotoxic regimens for aBC was two and four, respectively. Confirmed ORR was 21% (95% CI, 10 to 35) (cohort 1) and 37% (95% CI, 22 to 55) (cohort 2). Median duration of response was 5.8 and 3.8 months, respectively. Confirmed ORR was 23% (BRCA1), 33% (BRCA2), 26% (TNBC) and 29% (hormone receptor positive). The most common allgrade adverse events (AEs) included anemia (52%), fatigue (45%), and nausea (42%). Talazoparib-related AEs led to drug discontinuation in three (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 aBC and germline BRCA mutation.

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