TALA is a dual-mechanism PARP inhibitor that traps PARP on DNA, prevents DNA damage repair, and causes cell death in BRCA1/2-mutated cells.
EMBRACA is an open-label, randomized, 2-arm phase 3 trial comparing the efficacy and safety of TALA (1 mg/day) with standard single-agent PCT (capecitabine, eribulin, gemcitabine, or vinorelbine) in pts with aBC and a gBRCAm). In this analysis clinical outcomes were assessed in BRCA1 and BRCA2 subgroups.
Of 431 pts randomized, 196 were BRCA1 (133 TALA; 63 PCT), 235 were BRCA2 (154 TALA; 81 PCT). Mean (SD) age was 45.4 (11.66) years (BRCA1) and 50.4 (11.45) years (BRCA2). Pts in all groups had received a median of 1 prior cytotoxic regimen for aBC. TALA demonstrated a statistically significant improvement in both objective response rate (odds ratio [OR] [95% CI] BRCA1 7.01 [2.99-19.54]; BRCA2 4.15 [1.90-8.52]; both P<.0001) and progression-free survival (hazard ratio [95% CI] BRCA1 0.59 [0.39-0.90]; BRCA2 0.47 [0.32-0.70]) in BRCA1 and BRCA2 subgroups compared with PCT. Mean (SD) duration of TALA therapy was 7.5 (7.07) mo (BRCA1) and 9.2 (6.88) mo (BRCA2), with 15% (BRCA1) and 22% (BRCA2) of pts receiving TALA for ≥12 mo. Median duration of response (DOR) to TALA was longest in BRCA2 pts (6.3 mo), followed by BRCA1 pts (4.2 mo); BRCA1 and BRCA2 pts receiving PCT had a DOR of approximately 3.0 mo. Pts on TALA achieved a clinical benefit rate at 24 weeks (BRCA1 62%; BRCA2 74%) with OR significantly favouring TALA over PCT in both groups. Of pts receiving TALA, anaemia was the most common adverse event (AE) in BRCA1 pts (56%) and fatigue in BRCA2 pts (50%). Serious AEs occurred in both BRCA1 and BRCA2 pts (32%) receiving TALA.
In pts with advanced gBRCAm breast cancer, TALA demonstrated statistically significant improvements in clinical outcomes for both BRCA1 and BRCA2 subgroups compared with PCT.
Clinical trial identification
Legal entity responsible for the study
his study was sponsored by Medivation LLC, a Pfizer company.
Editorial and medical writing support funded by Pfizer Inc. were provided by Edwin Thrower, PhD, Mary Kacillas and Paula Stuckart of Ashfield Healthcare Communications, Middletown, Connecticut.
H.S. Rugo: Fees for contracted research to the University of California: Eisai, Genentech, GSK, Lilly, Macrogenics, Merck, Novartis, OBI Pharma, Pfizer, Plexxikon; Travel: Lilly, Mylan, Puma. J. Ettl: Consulting fees: Novartis, Pfizer, Roche, and Eisai; Contracted research: Celgene; Honoraria: Pfizer, Roche, Teva, Pierre Fabre. S.A. Hurvitz: Contracted research: Amgen, Bayer, BioMarin, BI, Cascadian Therapeutics, Dignitana, Genentech/Roche, GSK, Lilly, Medivation, Merrimack, Novartis, OBI Pharma, Pfizer, Puma Biotechnology, Sanofi; Travel: Bayer, Lilly, Novartis, OBI Pharma. Martín: Consulting fees: Pfizer and fees for non-CME services received directly from commercial interests or their agents: Pfizer. M. Al-Adhami, I.C. Tudor: Employment: Pfizer, Inc. J.L. Blum: Consulting fees: Pfizer. A.L. Hannah: Consulting fees: Basilea, Medivation/Pfizer and Nektar; Ownership interest: NeoGenomics Laboratories. J.K. Litton: Institutional-contracted research: Pfizer, Novartis, EMD-Serono, AstraZeneca, GlaxoSmithKline, Genentech; Advisory board participation: AstraZeneca and Pfizer, both uncompensated. All other authors have declared no conflicts of interest.