A phase II study of talazoparib after platinum or cytotoxic nonplatinum regimens in patients with advanced breast cancer and germline BRCA1/2 mutations (ABRAZO) Journal Article


Authors: 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.; on behalf of the ABRAZO Study Group
Article Title: A phase II study of talazoparib after platinum or cytotoxic nonplatinum regimens in patients with advanced breast cancer and germline BRCA1/2 mutations (ABRAZO)
Abstract: Purpose: To assess talazoparib activity in germline BRCA1/2 mutation carriers with advanced breast cancer. Patients and Methods: 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 advanced breast cancer. Primary endpoint was confirmed objective response rate (ORR) by independent radiological assessment. Results: We enrolled 84 patients (cohort 1, n 1⁄4 49; cohort 2, n 1⁄4 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% (BRCA1), 33% (BRCA2), 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). Conclusions: Talazoparib exhibited promising antitumor activity in patients with advanced breast cancer and germline BRCA mutation. © 2018 American Association for Cancer Research.
Journal Title: Clinical Cancer Research
Volume: 25
Issue: 9
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2019-05-01
Start Page: 2717
End Page: 2724
Language: English
DOI: 10.1158/1078-0432.Ccr-18-1891
PUBMED: 30563931
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 3 June 2019 -- Source: Scopus
Altmetric
Citation Impact
MSK Authors
  1. Mark E Robson
    488 Robson