PMID- 33781053 OWN - NLM STAT- MEDLINE DCOM- 20220207 LR - 20240403 IS - 2005-9256 (Electronic) IS - 1598-2998 (Print) IS - 1598-2998 (Linking) VI - 53 IP - 4 DP - 2021 Oct TI - Talazoparib Versus Chemotherapy in Patients with HER2-negative Advanced Breast Cancer and a Germline BRCA1/2 Mutation Enrolled in Asian Countries: Exploratory Subgroup Analysis of the Phase III EMBRACA Trial. PG - 1084-1095 LID - 10.4143/crt.2020.1381 [doi] AB - PURPOSE: We evaluated study outcomes in patients enrolled in Asian regions in the phase III EMBRACA trial of talazoparib vs. chemotherapy. MATERIALS AND METHODS: Patients with human epidermal growth factor receptor 2-negative germline BRCA1/2-mutated advanced breast cancer who received prior chemotherapy were randomized 2:1 to talazoparib 1 mg/day or chemotherapy (physician's choice). Primary endpoint was progression-free survival (PFS) per independent central review in the intent-to-treat (ITT) population. This post-hoc analysis evaluated efficacy/safety endpoints in the ITT population of patients enrolled in Asian regions. RESULTS: Thirty-three patients were enrolled at Asian sites (talazoparib, n=23; chemotherapy, n=10). Baseline characteristics were generally comparable with the overall EMBRACA population. In Asian patients, median PFS was 9.0 months (95% confidence interval [CI], 3.0 to 15.2) for talazoparib and 7.1 months (95% CI, 1.2 to not reached) for chemotherapy (hazard ratio [HR], 0.74 [95% CI, 0.22 to 2.44]). Objective response rate was numerically higher for talazoparib vs. chemotherapy (62.5% [95% CI, 35.4 to 84.8] vs. 25.0% [95% CI, 3.2 to 65.1]). Median overall survival was 20.7 months (95% CI, 9.4 to 40.1) versus 21.2 months (95% CI, 2.7 to 35.0) (HR, 1.41 [95% CI, 0.49 to 4.05]). In Asian patients, fewer grade 3/4 adverse events (AEs), serious AEs (SAEs), grade 3/4 SAEs, and AEs resulting in dose reduction/discontinuation occurred with talazoparib than chemotherapy; for talazoparib, the frequency of these events was lower in Asian patients versus overall EMBRACA population. CONCLUSION: In this subgroup analysis, talazoparib numerically improved efficacy versus chemotherapy and was generally well tolerated in Asian patients, with fewer grade 3/4 treatment-emergent AE (TEAEs), SAEs, and TEAEs leading to dose modification vs. the overall EMBRACA population. FAU - Lee, Kyung-Hun AU - Lee KH AD - Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. FAU - Sohn, Joohyuk AU - Sohn J AD - Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea. FAU - Goodwin, Annabel AU - Goodwin A AD - Concord Repatriation General Hospital, Concord, NSW, Australia. FAU - Usari, Tiziana AU - Usari T AD - Pfizer, Milan, Italy. FAU - Lanzalone, Silvana AU - Lanzalone S AD - Pfizer, Milan, Italy. FAU - Im, Seock-Ah AU - Im SA AD - Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. FAU - Kim, Sung-Bae AU - Kim SB AD - Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. LA - eng GR - Pfizer/ GR - Medivation/ PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20210324 PL - Korea (South) TA - Cancer Res Treat JT - Cancer research and treatment JID - 101155137 RN - 0 (BRCA1 Protein) RN - 0 (BRCA1 protein, human) RN - 0 (BRCA2 Protein) RN - 0 (BRCA2 protein, human) RN - 0 (Furans) RN - 0 (Ketones) RN - 0 (Phthalazines) RN - 0W860991D6 (Deoxycytidine) RN - 6804DJ8Z9U (Capecitabine) RN - 9QHX048FRV (talazoparib) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - LR24G6354G (eribulin) RN - Q6C979R91Y (Vinorelbine) RN - 0 (Gemcitabine) SB - IM MH - Adult MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Asia MH - BRCA1 Protein/*genetics MH - BRCA2 Protein/*genetics MH - Breast Neoplasms/*drug therapy/genetics/metabolism/pathology MH - Capecitabine/administration & dosage MH - Deoxycytidine/administration & dosage/analogs & derivatives MH - Female MH - Follow-Up Studies MH - Furans/administration & dosage MH - *Germ-Line Mutation MH - Humans MH - Ketones/administration & dosage MH - Middle Aged MH - Phthalazines/administration & dosage MH - Prognosis MH - Receptor, ErbB-2/*metabolism MH - Survival Rate MH - Vinorelbine/administration & dosage MH - Gemcitabine PMC - PMC8524025 OTO - NOTNLM OT - Asian OT - BRCA1/2 mutation OT - Breast neoplasms OT - HER2-negative OT - PARP inhibitor OT - Phase III OT - Talazoparib COIS- Conflicts of Interest Kyung-Hun Lee reports honoraria from Roche and AstraZeneca, and has participated in advisory boards for Bayer, Ono Pharmaceutical, Samsung Bioepis, Roche, Eisai, and AstraZeneca. Sung-Bae Kim reports research funding from Novartis, Sanofi-Aventis, and DongKook Pharm Co., and has participated as a consultant in advisory boards for Novartis, AstraZeneca, Lilly, Dae Hwa Pharmaceutical Co. Ltd, ISU Abxis, and Daiichi-Sankyo. Joohyuk Sohn reports research grant/funding from MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, Bayer, GSK, CONTESSA, and Daiichi-Sankyo. Annabel Goodwin reports honoraria from AstraZeneca and Pfizer for participation in advisory boards. Tiziana Usari and Silvana Lanzalone are employees of Pfizer. Seock-Ah Im reports research funding from AstraZeneca, Eisai, Roche, Pfizer, and Daewoong Pharm Co., and has participated as a consultant in advisory boards for AstraZeneca, Amgen, Hanmi, Eisai, GSK, Idience, Lilly, MSD, Novartis, Daiichi-Sankyo, Roche, and Pfizer. EDAT- 2021/03/31 06:00 MHDA- 2022/02/08 06:00 PMCR- 2021/10/01 CRDT- 2021/03/30 04:22 PHST- 2020/12/30 00:00 [received] PHST- 2021/03/21 00:00 [accepted] PHST- 2021/03/31 06:00 [pubmed] PHST- 2022/02/08 06:00 [medline] PHST- 2021/03/30 04:22 [entrez] PHST- 2021/10/01 00:00 [pmc-release] AID - crt.2020.1381 [pii] AID - crt-2020-1381 [pii] AID - 10.4143/crt.2020.1381 [doi] PST - ppublish SO - Cancer Res Treat. 2021 Oct;53(4):1084-1095. doi: 10.4143/crt.2020.1381. Epub 2021 Mar 24.