{"doi":"10.1016/j.annonc.2020.08.2098","title":"Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial","abstract":"•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. BackgroundIn 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 methodsThis 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.ResultsA 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.ConclusionsIn 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 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 mon","journal":"Annals of Oncology","year":2020,"id":48525,"datarank":0.8994678132928533,"base_score":5.996452088619021,"endowment":5.996452088619021,"self_citation_contribution":0.8994678132928533,"citation_network_contribution":0.0,"self_endowment_contribution":0.8994678132928533,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":401,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":37110,"name":"Sara A. Hurvitz","orcid":"0000-0001-7808-7191","position":1,"is_corresponding":false},{"id":230220,"name":"Lida A. Mina","orcid":"0000-0003-2606-9922","position":2,"is_corresponding":false},{"id":34069,"name":"Hope S. Rugo","orcid":"0000-0001-6710-4814","position":3,"is_corresponding":false},{"id":230221,"name":"Ki Hoon Lee","orcid":"0000-0002-8229-3462","position":4,"is_corresponding":false},{"id":230222,"name":"Anthony Gonçalvès","orcid":"0000-0001-7570-7439","position":5,"is_corresponding":false},{"id":233980,"name":"Sami Diab","orcid":null,"position":6,"is_corresponding":false},{"id":230223,"name":"Natasha Woodward","orcid":"0000-0003-0944-4807","position":7,"is_corresponding":false},{"id":230224,"name":"Annabel Goodwin","orcid":"0000-0002-8859-9980","position":8,"is_corresponding":false},{"id":230225,"name":"Rinat Yerushalmi","orcid":"0000-0001-6221-2859","position":9,"is_corresponding":false},{"id":233981,"name":"Henri Roché","orcid":null,"position":10,"is_corresponding":false},{"id":230226,"name":"Young‐Hyuck Im","orcid":"0000-0001-6459-8118","position":11,"is_corresponding":false},{"id":81077,"name":"W. Eiermann","orcid":null,"position":12,"is_corresponding":false},{"id":230227,"name":"Ruben G.W. Quek","orcid":"0000-0001-9602-3239","position":13,"is_corresponding":false},{"id":233982,"name":"Tiziana Usari","orcid":null,"position":14,"is_corresponding":false},{"id":233983,"name":"Silvana Lanzalone","orcid":null,"position":15,"is_corresponding":false},{"id":233984,"name":"Akos Czibere","orcid":null,"position":16,"is_corresponding":false},{"id":230228,"name":"Joanne L. Blum","orcid":"0000-0002-7951-6645","position":17,"is_corresponding":false},{"id":218786,"name":"Miguel Martín","orcid":null,"position":18,"is_corresponding":false},{"id":230229,"name":"Johannes Ettl","orcid":"0000-0003-4754-8447","position":19,"is_corresponding":false},{"id":230219,"name":"Jennifer K. Litton","orcid":"0000-0001-8390-4985","position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T20:35:18.908826Z","pmid":"32828825","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}