Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial

• Published in: Annals of oncology Vol. 31; no. 11; pp. 1526 - 1535
• Main Authors: Litton, J.K., Hurvitz, S.A., Mina, L.A., Rugo, H.S., Lee, K.-H., Gonçalves, A., Diab, S., Woodward, N., Goodwin, A., Yerushalmi, R., Roché, H., Im, Y.-H., Eiermann, W., Quek, R.G.W., Usari, T., Lanzalone, S., Czibere, A., Blum, J.L., Martin, M., Ettl, J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2020
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; BRCA1 Protein - genetics; breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Germ Cells; Germ-Line Mutation; germline BRCA mutation; Humans; overall survival; PARP inhibitor; Phthalazines; Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use; Quality of Life; talazoparib; germline BRCA mutation; overall survival; breast cancer; talazoparib; PARP inhibitor
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1016/j.annonc.2020.08.2098

In EMBRACA, talazoparib prolonged progression-free survival versus chemotherapy (hazard ratio [HR] 0.542 [95% confidence interval (CI) 0.413-0.711]; P < 0.0001) and improved patient-reported outcomes (PRO) in germline BRCA1/2 (gBRCA1/2)-mutated advanced breast cancer (ABC). We report final overall survival (OS). This randomized phase III trial enrolled patients with gBRCA1/2-mutated HER2-negative ABC. Patients received talazoparib or physician's choice of chemotherapy. OS was analyzed using stratified HR and log-rank test and prespecified rank-preserving structural failure time model to account for subsequent treatments. A total of 431 patients were entered in a randomized study (287 talazoparib/144 chemotherapy) with 412 patients treated (286 talazoparib/126 chemotherapy). By 30 September 2019, 216 deaths (75.3%) occurred for talazoparib and 108 (75.0%) chemotherapy; median follow-up was 44.9 and 36.8 months, respectively. HR for OS with talazoparib versus chemotherapy was 0.848 (95% CI 0.670-1.073; P = 0.17); median (95% CI) 19.3 months (16.6-22.5 months) versus 19.5 months (17.4-22.4 months). Kaplan–Meier survival percentages (95% CI) for talazoparib versus chemotherapy: month 12, 71% (66% to 76%)/74% (66% to 81%); month 24, 42% (36% to 47%)/38% (30% to 47%); month 36, 27% (22% to 33%)/21% (14% to 29%). Most patients received subsequent treatments: for talazoparib and chemotherapy, 46.3%/41.7% received platinum and 4.5%/32.6% received a poly(ADP-ribose) polymerase (PARP) inhibitor, respectively. Adjusting for subsequent PARP and/or platinum use, HR for OS was 0.756 (95% bootstrap CI 0.503-1.029). Grade 3-4 adverse events occurred in 69.6% (talazoparib) and 64.3% (chemotherapy) patients, consistent with previous reports. Extended follow-up showed significant overall improvement and delay in time to definitive clinically meaningful deterioration in global health status/quality of life and breast symptoms favoring talazoparib versus chemotherapy (P < 0.01 for all), consistent with initial analyses. In gBRCA1/2-mutated HER2-negative ABC, talazoparib did not significantly improve OS over chemotherapy; subsequent treatments may have impacted analysis. Safety was consistent with previous observations. PRO continued to favor talazoparib. •In BRCA1/2-mutated advanced breast cancer, talazoparib did not significantly improve overall survival (OS) versus chemotherapy.•OS was generally consistent across subgroups including by prior platinum, hormone-receptor status, or line of treatment.•Most patients received subsequent systemic treatments, which may have confounded the survival outcome.•Toxicities were managed by supportive care medication/dose modifications; safety was consistent with previous observations.•Extended follow-up of patient-reported outcomes continued to favor talazoparib over chemotherapy.