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- Title:
Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial.
- Document type:
- Article; Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
- Author(s):
- 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
- Abstract:
- BACKGROUND: 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). PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
- Journal title abbreviation:
- Ann Oncol
- Year:
- 2020
- Journal volume:
- 31
- Journal issue:
- 11
- Pages contribution:
- 1526-1535
- Fulltext / DOI:
- doi:10.1016/j.annonc.2020.08.2098
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/32828825
- Print-ISSN:
- 0923-7534
- TUM Institution:
- Frauenklinik und Poliklinik
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