PMID- 35907135 OWN - NLM STAT- MEDLINE DCOM- 20221025 LR - 20221025 IS - 1880-4233 (Electronic) IS - 1340-6868 (Print) IS - 1340-6868 (Linking) VI - 29 IP - 6 DP - 2022 Nov TI - Efficacy and safety of talazoparib in Japanese patients with germline BRCA-mutated locally advanced or metastatic breast cancer: results of the phase 1 dose-expansion study. PG - 1088-1098 LID - 10.1007/s12282-022-01390-w [doi] AB - BACKGROUND: Talazoparib, a poly(ADP-ribose) polymerase enzyme inhibitor, is approved for the treatment of patients with germline BRCA1/2 (gBRCA1/2)-mutated HER2-negative advanced breast cancer. This two-part study, a recently published dose-escalation part followed by the dose-expansion part reported here, evaluated the efficacy and safety of talazoparib in Japanese patients with gBRCA1/2-mutated advanced breast cancer. METHODS: In this open-label, multicenter phase 1 study (NCT03343054), the primary endpoint of the dose-expansion part was confirmed objective response rate (ORR), determined by investigator assessment (RECIST 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Patients received the recommended phase 2 dose (1 mg/day; 0.75 mg/day moderate renal impairment). RESULTS: Nineteen Japanese patients with gBRCA1/2-mutated locally advanced or metastatic breast cancer were enrolled. Confirmed ORR was 57.9% (11/19; 90% confidence interval [CI] 36.8-77.0). Stable disease was observed in 36.8% (7/19) of patients. Per investigator assessment, median PFS was 7.2 months (95% CI 4.1-not estimable) and 12-month OS rate was 84.7% (90% CI 57.5-95.1). Median OS was not reached; 17/19 patients were alive and censored at 12 months. All patients experienced treatment-related adverse events (AEs); the majority were hematologic. The most common treatment-related AE was anemia (68.4%; [13/19]). Grade 3/4 treatment-related AEs were observed in 52.6% (10/19) of patients. During the safety period, there were no grade 5 treatment-emergent AEs, treatment-related serious AEs, or deaths. CONCLUSIONS: In Japanese patients with gBRCA mutations and locally advanced or metastatic breast cancer, talazoparib monotherapy was generally well tolerated and resulted in clinically meaningful ORRs. GOV IDENTIFIER: NCT03343054. CI - (c) 2022. The Author(s). FAU - Kotani, Haruru AU - Kotani H AUID- ORCID: 0000-0002-0355-9294 AD - Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. k.haruru@aichi-cc.jp. FAU - Masuda, Norikazu AU - Masuda N AUID- ORCID: 0000-0002-7302-0278 AD - National Hospital Organization Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka-shi, Osaka, 540-0006, Japan. AD - Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. FAU - Yamashita, Toshinari AU - Yamashita T AUID- ORCID: 0000-0002-6479-1660 AD - Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan. FAU - Naito, Yoichi AU - Naito Y AUID- ORCID: 0000-0002-8490-9064 AD - National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. FAU - Taira, Tetsuhiko AU - Taira T AUID- ORCID: 0000-0002-3091-8168 AD - Hakuaikai Medical Corporation Sagara Hospital, 3-31 Matsubara-cho Kagoshima, Kagoshima, 892-0833, Japan. FAU - Inoue, Kenichi AU - Inoue K AUID- ORCID: 0000-0003-2686-8732 AD - Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan. FAU - Takahashi, Masato AU - Takahashi M AUID- ORCID: 0000-0002-6641-9598 AD - National Hospital Organization Hokkaido Cancer Center, Kikusui 4-jo 2-chome 3-54 Shiroishi-ku, Sapporo, Hokkaido, 003-0804, Japan. FAU - Yonemori, Kan AU - Yonemori K AD - National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. FAU - Toyoizumi, Shigeyuki AU - Toyoizumi S AUID- ORCID: 0000-0002-7011-5263 AD - Pfizer R&D Japan, Shinjuku Bunka Quint Bldg. 3-22-7, Yoyogi, Shibuya-ku, Tokyo, 151-0053, Japan. FAU - Mori, Yuko AU - Mori Y AUID- ORCID: 0000-0003-1919-2463 AD - Pfizer R&D Japan, Shinjuku Bunka Quint Bldg. 3-22-7, Yoyogi, Shibuya-ku, Tokyo, 151-0053, Japan. FAU - Nagasawa, Takashi AU - Nagasawa T AUID- ORCID: 0000-0002-1600-1062 AD - Pfizer R&D Japan, Shinjuku Bunka Quint Bldg. 3-22-7, Yoyogi, Shibuya-ku, Tokyo, 151-0053, Japan. FAU - Hori, Natsuki AU - Hori N AUID- ORCID: 0000-0003-4675-3975 AD - Pfizer R&D Japan, Shinjuku Bunka Quint Bldg. 3-22-7, Yoyogi, Shibuya-ku, Tokyo, 151-0053, Japan. FAU - Iwata, Hiroji AU - Iwata H AD - Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. LA - eng SI - ClinicalTrials.gov/NCT03343054 PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study DEP - 20220730 PL - Japan TA - Breast Cancer JT - Breast cancer (Tokyo, Japan) JID - 100888201 RN - 9QHX048FRV (talazoparib) RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors) RN - 0 (Antineoplastic Agents) RN - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) SB - IM MH - Humans MH - Female MH - *Breast Neoplasms/drug therapy/genetics/pathology MH - Japan MH - Germ-Line Mutation MH - Poly(ADP-ribose) Polymerase Inhibitors/adverse effects MH - *Antineoplastic Agents/therapeutic use MH - Germ Cells/pathology MH - Poly(ADP-ribose) Polymerases PMC - PMC9587945 OTO - NOTNLM OT - BRCA OT - Breast cancer OT - Japanese patients OT - PARP inhibitor OT - Talazoparib COIS- Haruru Kotani has no disclosures to report. Norikazu Masuda reports honoraria from AstraZeneca, Chugai, Eisai, Eli Lilly, and Pfizer; research funding to their institution from AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa Kirin, MSD, Novartis, Pfizer, and Sanofi; and is on the board of directors for the Japanese Breast Cancer Society and JBCRG (Japan Breast Cancer Research Group Association). Toshinari Yamashita reports research funding to their institution from Chugai, Kyowa Kirin, Nippon Kayaku, and Taiho; and honoraria from AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa Kirin, Nippon Kayaku, Novartis Pharma, Pfizer Japan, and Taiho. Yoichi Naito reports participation in the speaker's bureau for AstraZeneca, Bayer, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Eli Lilly, Nippon Kayaku, Novartis, Pfizer, Roche Diagnostics, and Taiho; and research funding from Roche Diagnostics. Tetsuhiko Taira reports honoraria from Chugai, Daiichi Sankyo, Eli Lilly, Kyowa Kirin, Novartis, and Taiho. Kenichi Inoue reports honoraria from Chugai; and research funding to their institution from AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, MSD, Pfizer, and Sanofi. Masato Takahashi reports honoraria from AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, and Pfizer; and research funding to their institution from Kyowa Kirin and Taiho. Kan Yonemori reports honoraria from AstraZeneca, Chugai, Eisai, Eli Lilly, Pfizer, and Takeda; advisor fees from Chugai, Eisai, Novartis, Ono, and Takeda; and research funding to their institution from AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Genmab, Kyowa Kirin, Taiho, Takeda, MSD, Nihon-Kayaku, Novartis, Pfizer, and Sanofi. Shigeyuki Toyoizumi, Yuko Mori, Takashi Nagasawa, and Natsuki Hori report salary and ownership interest for Pfizer. Hiroji Iwata reports research funding from Chugai, Lilly, MSD, and Novartis; honoraria from AstraZeneca, Chugai, and Daiichi Sankyo; and participation in advisory boards for AstraZeneca, Chugai, Daiichi Sankyo, Kyowa Hakko Kirin, Lilly, Novartis, and Pfizer. EDAT- 2022/07/31 06:00 MHDA- 2022/10/26 06:00 PMCR- 2022/07/30 CRDT- 2022/07/30 11:18 PHST- 2022/04/27 00:00 [received] PHST- 2022/07/10 00:00 [accepted] PHST- 2022/07/31 06:00 [pubmed] PHST- 2022/10/26 06:00 [medline] PHST- 2022/07/30 11:18 [entrez] PHST- 2022/07/30 00:00 [pmc-release] AID - 10.1007/s12282-022-01390-w [pii] AID - 1390 [pii] AID - 10.1007/s12282-022-01390-w [doi] PST - ppublish SO - Breast Cancer. 2022 Nov;29(6):1088-1098. doi: 10.1007/s12282-022-01390-w. Epub 2022 Jul 30.