A Phase II Study of Talazoparib After Platinum or Cytotoxic Nonplatinum Regimens in Patients With Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO).

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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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