Switch maintenance endocrine therapy plus bevacizumab after bevacizumab plus paclitaxel in advanced or metastatic oestrogen receptor-positive, HER2-negative breast cancer (BOOSTER): a randomised, open-label, phase 2 trial.

Autor:	Saji S; Department of Medical Oncology, Fukushima Medical University Hospital, Fukushima, Japan. Electronic address: ss-saji@wa2.so-net.ne.jp., Taira N; Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan., Kitada M; Breast Disease Center, Asahikawa Medical University Hospital, Hokkaido, Japan., Takano T; Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan., Takada M; Department of Breast Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan., Ohtake T; Department of Breast Surgery, Fukushima Medical University Hospital, Fukushima, Japan., Toyama T; Department of Breast Surgery, Nagoya University Graduate School of Medical Sciences, Nagoya, Japan., Kikawa Y; Department of Breast Surgery, Kobe City Medical Center General Hospital, Hyogo, Japan., Hasegawa Y; Department of Breast Surgery, Hachinohe City Hospital, Aomori, Japan., Fujisawa T; Department of Breast Oncology, Gunma Prefectural Cancer Center, Gunma, Japan., Kashiwaba M; Department of Breast Surgery, Adachi Breast Clinic, Kyoto, Japan., Ishida T; Department of Breast and Endocrine Surgical Oncology, Tohoku University Hospital, Miyagi, Japan., Nakamura R; Division of Breast Surgery, Chiba Cancer Center, Chiba, Japan., Yamamoto Y; Department of Breast and Endocrine Surgery, Kumamoto University Hospital, Kumamoto, Japan., Toh U; Department of Breast Surgery, Kurume University Hospital, Fukuoka, Japan., Iwata H; Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan., Masuda N; Department of Breast and Endocrine Surgery, Nagoya City University Graduate School of Medicine, Nagoya, Japan., Morita S; Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan., Ohno S; Breast Oncology Center, Cancer Institute Hospital of JFCR, Tokyo, Japan., Toi M; Department of Breast Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Jazyk:	angličtina
Zdroj:	The Lancet. Oncology [Lancet Oncol] 2022 May; Vol. 23 (5), pp. 636-649. Date of Electronic Publication: 2022 Apr 08.
DOI:	10.1016/S1470-2045(22)00196-6
Abstrakt:	Background: Anticancer treatment regimens typically cause unpleasant side-effects. We aimed to investigate the benefit of switch maintenance endocrine therapy plus bevacizumab after fixed cycles of first-line induction chemotherapy with weekly paclitaxel plus bevacizumab in patients with oestrogen receptor (ER)-positive, HER2-negative advanced or metastatic breast cancer. Methods: BOOSTER was a prospective, open-label, multicentre, randomised, controlled, phase 2 study done in 53 hospitals in Japan. Eligible patients were women aged 20-75 years, with an Eastern Cooperative Oncology Group performance status of 0-1, who had not received chemotherapy for ER-positive, HER2-negative advanced or metastatic breast cancer. All patients received four to six cycles (in which 4 weeks of treatment constitute one cycle) of weekly paclitaxel plus bevacizumab induction therapy (weekly paclitaxel 90 mg/m 2 , administered intravenously on days 1, 8, and 15 of each cycle, plus bevacizumab 10 mg/kg administered intravenously on days 1 and 15 of each cycle; first registration). Patients with a complete response, partial response, or stable disease after induction therapy (responders) were then randomly assigned (1:1) using the randomisation enrolment form to either continue weekly paclitaxel plus bevacizumab or switch to maintenance endocrine therapy (an aromatase inhibitor or fulvestrant with or without ovarian-function suppression) plus bevacizumab. Randomisation was stratified by induction therapy period, response to induction therapy, age, history of endocrine therapy, and study site. Patients could receive weekly paclitaxel plus bevacizumab reinduction if they had disease progression with maintenance endocrine therapy plus bevacizumab. The primary endpoint was time to failure of strategy (TFS). Efficacy and safety analyses were done in all treated patients (full analysis set). This study is registered with ClinicalTrials.gov, NCT01989780, and registration and follow-up are closed. Findings: Between Jan 1, 2014, and Dec 31, 2015, we enrolled 160 patients who began weekly paclitaxel plus bevacizumab induction therapy. 125 (78%) patients (responders) were randomly assigned to endocrine therapy plus bevacizumab (n=62; n=61 in the full analysis set) or weekly paclitaxel plus bevacizumab (n=63; n=63 in the full analysis set). Among 61 patients in the switch maintenance endocrine therapy plus bevacizumab group, 32 (52%) were reinitiated on weekly paclitaxel plus bevacizumab. At a median follow-up of 21·3 months (IQR 13·0-28·2), TFS was significantly longer in the endocrine therapy plus bevacizumab group than in the weekly paclitaxel plus bevacizumab group (median 16·8 months [95% CI 12·9-19·0] vs 8·9 months [5·7-13·8]; hazard ratio 0·51 [0·34-0·75]; p=0·0006). The most common grade 3-4 non-haematological adverse events after randomisation were proteinuria (in ten [16%] of 61 patients in the endocrine therapy plus bevacizumab group vs eight [13%] of 63 patients in the weekly paclitaxel plus bevacizumab group), hypertension (six [10%] vs six [10%]), and peripheral neuropathy (one [2%] vs six [10%]). One treatment-related death was reported in the weekly paclitaxel plus bevacizumab group (duodenal ulcer perforation). Interpretation: Switch to maintenance endocrine therapy plus bevacizumab with the possibility of weekly paclitaxel reinduction if needed is an efficacious alternative, with a better safety profile, to continuing weekly paclitaxel plus bevacizumab in patients with ER-positive, HER2-negative advanced or metastatic breast cancer who have responded to induction therapy. Funding: Chugai Pharmaceutical. Translation: For the Japanese translation of the abstract see Supplementary Materials section. Competing Interests: Declaration of interests SS reports institutional grants from Eisai, Takeda Pharmaceutical, Novartis Pharma KK, and Eli Lilly Japan KK; institutional grants and contracted clinical trials from Taiho Pharmaceutical and Chugai Pharmaceutical; contracted clinical trials from MSD KK, AstraZeneca KK, and Daiichi Sankyo; personal fees from Chugai Pharmaceutical, Kyowa Kirin KK, MSD KK, Novartis Pharma KK, Eisai, Takeda Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan KK, AstraZeneca KK, Pfizer Japan, Taiho Pharmaceutical, and Nippon Kayaku; and personal fees for participation on a data safety monitoring board or advisory board from Chugai Pharmaceutical/Roche, AstraZeneca KK, Eli Lilly Japan KK, Pfizer Japan, Kyowa Kirin KK, Daiichi Sankyo, and Novartis Pharma KK; and has served as an executive board member of the Japan Breast Cancer Research Group (JBCRG) and the Japanese Breast Cancer Society (JBCS). NT reports personal fees from Eisai, Kyowa Kirin KK, Pfizer Japan, and AstraZeneca KK. TTa reports institutional grants from Chugai Pharmaceutical, Daiichi Sankyo, Ono Pharmaceutical, MSD KK, and Eisai; and honoraria for lectures from Chugai Pharmaceutical, Daiichi Sankyo, Eisai Co, Kyowa Kirin KK, Pfizer Japan, Eli Lilly Japan KK, and Celltrion Healthcare. MTa reports institutional grants from Daiichi Sankyo, AstraZeneca KK, Medbis, and Yakult Honsha; and personal fees from Chugai Pharmaceutical, Eisai, Daiichi Sankyo, Eli Lilly Japan KK, Pfizer Japan, AstraZeneca KK, Nippon Kayaku, and Mitaka Kohki KK. TO reports institutional grants from Eisai, Taiho Pharmaceutical, Takeda Pharmaceutical, Eli Lilly Japan KK, Asahi Kasei Pharma Corporation, Nippon Kayaku, Kyowa Kirin KK, and Astellas Pharma; institutional grants and contracted clinical trials from Chugai Pharmaceutical and Daiichi Sankyo; contracted clinical trials from MSD KK and Maruho; and personal fees from Chugai Pharmaceutical, AstraZeneca KK, Pfizer Japan, Eisai, Daiichi Sankyo, Eli Lilly Japan KK, Novartis Pharma KK, MSD KK, Nippon Kayaku, Takeda Pharmaceutical, and Kyowa Kirin KK. TTo reports institutional grants from Eli Lilly Japan KK, Chugai Pharmaceutical, Eisai, Takeda Pharmaceutical, Kyowa Kirin KK, Daiichi Sankyo, and Nippon Kayaku; personal fees for consultation from Daiichi Sankyo; and personal fees from Daiichi Sankyo, Pfizer Japan, Novartis Pharma KK, AstraZeneca KK, Chugai Pharmaceutical, and Takeda Pharmaceutical. YK reports personal fees from Pfizer Japan, Eisai, Novartis Pharma KK, Eli Lilly Japan KK, and AstraZeneca KK in the past 36 months. MKa reports personal fees from Chugai Pharmaceutical, Eli Lilly Japan KK, Pfizer Japan, and Kyowa Kirin KK in the past 36 months. TI reports institutional grants from Chugai Pharmaceutical, Taiho Pharmaceutical, Eisai, and Kyowa Kirin KK; and personal fees from Chugai Pharmaceutical, Pfizer Japan, AstraZeneca KK, and Daiichi Sankyo. RN reports personal fees from Chugai Pharmaceutical, Kyowa Kirin KK, Eli Lilly Japan KK, Nippon Kayaku, AstraZeneca KK, Novartis Pharma, and Eisai in the past 36 months. YY reports institutional research funding from Chugai Pharmaceutical, Kyowa Kirin KK, Eisai, Daiichi Sankyo, Nippon Kayaku, Taiho Pharmaceutical, Takeda Pharmaceutical, Eli Lilly Japan KK, Pfizer Japan, and Novartis Pharma KK; and honoraria for lectures (personal) from AstraZeneca KK, Chugai Pharmaceutical, Kyowa Kirin KK, Novartis Pharma KK, Eli Lilly Japan KK, Pfizer Japan, Daiichi Sankyo, Nippon Kayaku, Taiho Pharmaceutical, Eisai, and Takeda Pharmaceutical; has served on the advisory board (personal) for AstraZeneca KK, Chugai Pharmaceutical, Novartis Pharma KK, Eli Lilly Japan KK, Pfizer Japan, and Daiichi Sankyo; and has served on the board of directors for JBCRG and JBCS. UT reports institutional grants from Chugai Pharmaceutical, Taiho Pharmaceutical, Eisai, Daiichi Sankyo, Takeda Pharmaceutical, Nippon Kayaku, and Kyowa Kirin KK; and personal fees from Chugai Pharmaceutical, Kyowa Kirin KK, Pfizer Japan, Taiho Pharmaceutical, and Eli Lilly Japan KK. HI reports institutional grants from Chugai Pharmaceutical, Eli Lilly Japan KK, Nippon Kayaku, Daiichi Sankyo, AstraZeneca KK, Taiho Pharmaceutical, Pfizer Japan, MSD KK, Sanofi KK, Novartis Pharma KK, Bayer Yakuhin, and Boehringer Ingelheim; consulting fees from Chugai Pharmaceutical, Kyowa Hakko Kirin, AstraZeneca KK, Eli Lilly Japan KK, Pfizer Japan, and Daiichi Sankyo; and personal fees from Chugai Pharmaceutical, AstraZeneca KK, Eli Lilly Japan KK, Pfizer Japan, Taiho Pharmaceutical, Daiichi Sankyo, Eisai, and Kyowa Hakko Kirin; and has served on the executive board for JBCRG. NM reports institutional grants from Chugai Pharmaceutical, Eli Lilly Japan KK, AstraZeneca KK, Pfizer Japan, Daiichi Sankyo, MSD KK, Eisai, Novartis Pharma KK, Sanofi KK, Kyowa Kirin KK, and Nippon Kayaku; and personal fees from Chugai Pharmaceutical, Pfizer Japan, AstraZeneca KK, Eli Lilly Japan KK, and Eisai; has served on the executive board for JBCRG (unpaid); and has served on the board of directors for JBCS (unpaid). SM reports institutional grants from Eisai; and personal fees from AstraZeneca KK, Bristol Myers Squibb KK, Chugai Pharmaceutical, Eli Lilly Japan KK, MSD KK, Eisai, Pfizer Japan, and Taiho Pharmaceutical. SO reports institutional grants from Eisai and Taiho Pharmaceutical; and personal fees from AstraZeneca KK, Chugai Pharmaceutical, Eisai, Eli Lilly Japan KK, and Pfizer Japan; and has served on the executive board for JBCRG. MTo reports institutional research grants from Chugai Pharmaceutical, Takeda Pharmaceutical, Pfizer Japan, Kyowa Kirin KK, Taiho Pharmaceutical, JBCRG, Eisai, Daiichi Sankyo, AstraZeneca KK, Astellas Pharma, Shimadzu Corporation, Yakult Honsha, Nippon Kayaku, AFI technology, Luxonus, and Shionogi; and honoraria for lectures or lecture chair (personal) from Chugai Pharmaceutical, Takeda Pharmaceutical, Pfizer Japan, Kyowa Kirin KK, Taiho Pharmaceutical, Eisai, Daiichi Sankyo, AstraZeneca KK, Eli Lilly Japan KK, MSD KK, Exact Sciences, Novartis Pharma KK, Konica Minolta, Shimadzu, Yakult Honsha, and Nippon Kayaku; has served on the advisory board for Kyowa Kirin KK, Daiichi Sankyo, Eli Lilly Japan KK, Konica Minolta, Bristol Myers Squibb KK, and Athenex Oncology; and has served as a member of the board of directors (no salary) for JBCRG, the Kyoto Breast Cancer Research Network, and the Organisation for Oncology and Translational Research. All other authors declare no competing interests. (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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