TALA is a dual-mechanism PARP inhibitor that prevents DNA damage repair by trapping PARP on DNA, resulting in cell death in BRCA1/2-mutated cells.
EMBRACA is an open-label, randomised, 2-arm phase 3 trial in which efficacy and safety of TALA (1 mg/day) is compared with standard single-agent PCT (capecitabine, eribulin, gemcitabine, or vinorelbine) in pts with aBC and gBRCAm. In this analysis clinical outcomes were assessed in 2 subgroups of pts who had either received prior platinum (PP) or had no prior platinum (NPP) treatment.
Of 431 pts randomised, 76 had PP in any setting (46 TALA; 30 PCT) and 355 were NPP (241 TALA; 114 PCT). Mean (SD) age was 46.4 (11.15) years. 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]: PP 3.16 [0.88-15.67], P=.0456; NPP 5.36 [2.89-9.89], P<.0001) and progression-free survival (hazard ratio [95% CI]: PP 0.76 [0.40-1.45], P=.41; NPP 0.52 [0.39-0.71], P<.0001) compared with PCT. Mean (SD) duration of TALA therapy was 7.2 (6.52) mo (PP) and 8.7 (7.09) mo (NPP), with 15% (PP) and 19% (NPP) of pts receiving TALA for ≥12 mo. Median duration of response (DOR) to TALA was longest in NPP pts (5.4 mo), followed by PP pts (4.2 mo); pts receiving PCT had a DOR of approximately 3.0 mo regardless of prior platinum status. Pts on TALA achieved a clinical benefit rate at 24 weeks (PP 59%; NPP 71%) with OR significantly favouring TALA over PCT in both groups. Of pts receiving TALA, nausea was the most common adverse event (AE) in PP pts (59%) and anaemia in NPP pts (53%). Serious AEs occurred in both PP (33%) and NPP pts (32%) taking TALA.
In pts with advanced gBRCAm breast cancer, TALA demonstrated statistically significant improvements in clinical outcomes for both PP and NPP subgroups compared with PCT. Although TALA treatment benefitted both groups, the benefit was greater if TALA was used before platinum therapy.
Clinical trial identification
Legal entity responsible for the study
This 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.
M. Martín: Consulting fees: Pfizer; Fees for non-CME services received directly from commercial interests or their agents: Pfizer. 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, Eisai; Contracted research: Celgene; Honoraria: Pfizer, Roche, Teva, and 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, and OBI Pharma. D. Markova, I.C. Tudor: Employee: Pfizer, Inc. J.L. Blum: Consulting fees: Pfizer. A.L. Hannah: Consulting fees: Basilea, Medivation/Pfizerand 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.