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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Date
2019-05-01ICR Author
Author
Turner, NC
Telli, ML
Rugo, HS
Mailliez, A
Ettl, J
Grischke, E-M
Mina, LA
Balmaña, J
Fasching, PA
Hurvitz, SA
Wardley, AM
Chappey, C
Hannah, AL
Robson, ME
ABRAZO Study Group,
Type
Journal Article
Metadata
Show full item recordAbstract
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 = 49; cohort 2, n = 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.
Collections
Subject
ABRAZO Study Group
Humans
Breast Neoplasms
Neoplasm Metastasis
Platinum
Phthalazines
BRCA1 Protein
BRCA2 Protein
Antineoplastic Combined Chemotherapy Protocols
Prognosis
Salvage Therapy
Cohort Studies
Follow-Up Studies
Drug Resistance, Neoplasm
Germ-Line Mutation
Adult
Aged
Middle Aged
Female
Poly(ADP-ribose) Polymerase Inhibitors
Research team
Molecular Oncology
Language
eng
Date accepted
2018-12-14
License start date
2019-05
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 2019, 25 (9), pp. 2717 - 2724
Publisher
AMER ASSOC CANCER RESEARCH
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