Safety and efficacy of nivolumab plus bevacizumab, paclitaxel for HER2-negative metastatic breast cancer: Primary results and biomarker data from a phase 2 trial (WJOG9917B)
- PMID: 35728379
- DOI: 10.1016/j.ejca.2022.05.014
Safety and efficacy of nivolumab plus bevacizumab, paclitaxel for HER2-negative metastatic breast cancer: Primary results and biomarker data from a phase 2 trial (WJOG9917B)
Abstract
Background: Preclinical models revealed potential synergistic effects of programmed cell death-1 inhibitors and anti-vascular endothelial growth factor (VEGF) antibodies. Therefore, we investigated the use of nivolumab, bevacizumab, and paclitaxel triple therapy for metastatic breast cancer.
Methods: This phase 2, multicentre, single-arm study (NEWBEAT) investigated the safety and efficacy of first-line nivolumab, paclitaxel, and bevacizumab in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer, regardless of programmed cell death-ligand 1 expression. The primary end-point was objective response rate. Key secondary end-points included progression-free survival, overall survival, and toxicities. A biomarker study evaluated tumour programmed cell death-ligand 1 expression and serum VEGF-A levels.
Results: Between February 2018 and October 2018, 57 patients were enrolled. An objective response rate was seen in 39/56 patients (70%, 95% confidence interval [CI]: 55.9-81.2%), meeting the primary end-point. The objective response rate was 74% in patients with hormone receptor-positive breast cancer versus 59% in patients with triple-negative breast cancer. The median progression-free survival and overall survival were 14.0 (95% CI 11.0-16.3) and 32.5 (95% CI 26.0-not evaluable) months, respectively (median follow-up: 29.5 months). Grade 3/4 adverse drug reactions occurred in 33 of 57 patients (58%). There were no grade 5 adverse events. Immune-related adverse events occurred in 43 of 57 patients (75%), with grade 3/4 events in eight patients (14%). Biomarker analysis showed that tumour programmed cell death-ligand 1 expression was not correlated with the efficacy of triple therapy. Efficacy outcomes were similar between the serum VEGF-high and VEGF-low groups.
Conclusions: First-line nivolumab, bevacizumab, and paclitaxel therapy showed promising efficacy and manageable toxicity in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer.
Keywords: Bevacizumab; Immunotherapy; Metastatic breast cancer; Nivolumab; VEGF.
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Conflict of interest statement Y. Ozaki reports research funds from Ono Pharmaceutical in relation to this work; and personal fees from Chugai outside the submitted work. J. Tsurutani reports research funds from Ono Pharmaceutical in relation to this work; grants from Daiichi Sankyo, Kyowa Kirin, Chugai, Pfizer, Eisai, Nippon Kayaku, and Eli Lilly; consulting fees from Asahi Kasei; lecture fees from Eisai, Chugai, Taiho, Daiichi Sankyo, Eli Lilly, Pfizer, Nippon Kayaku, Novartis, and AstraZeneca, support for attending meetings from Eisai and Daiichi Sankyo; and participation on advisory boards for Daiichi Sankyo, Eisai, AstraZeneca, and Eli Lilly outside the submitted work. T. Mukohara reports research funds from Ono Pharmaceutical in relation to this work; and grants from Daiichi Sankyo, Sysmex, MSD, Pfizer, Eisai, Chugai, Novartis, Sanofi, Seagen, and AstraZeneca; lecture fees from Eisai, Novartis, Chugai, Eli Lilly, AstraZeneca, and Kyowa Kirin outside the submitted work. T. Iwasa reports research funds from Ono Pharmaceutical in relation to this work. M. Takahashi reports research funds from Ono Pharmaceutical in relation to this work; and personal fees from AstraZeneca, Eli Lilly, Eisai, and Pfizer outside the submitted work. Y. Tanabe reports grants provided to the institution from Ono Pharmaceutical, outside of the submitted work. H. Kawabata reports research funds from Ono Pharmaceutical in relation to this work; and research funds from MSD, Daiichi Sankyo, Novartis, Taiho, and Chugai outside the submitted work. N. Masuda reports research funds from Ono Pharmaceutical in relation to this work; grants from Chugai and Eisai; personal fees, honoraria, and research funding provided to the institution from Chugai, AstraZeneca, Pfizer, Eli Lilly, Eisai, Takeda, Kyowa Kirin, Novartis, and Daiichi Sankyo; and research funding provided to the institution from MSD, Nippon Kayaku, and Sanofi outside of the submitted work. M. Futamura reports research funds from Ono Pharmaceutical in relation to this work; and personal fees from Chugai, Taiho, Takeda, Novartis, and Eisai outside the submitted work. H. Minami reports research funds from Ono Pharmaceutical in relation to this work; grants from Ono Pharmaceutical, Asahi Kasei Pharma, Astellas, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Sumitomo Dainippon, Eisai, Kyowa Kirin, Merck Serono, MSD, Nippon Shinyaku, Sanofi, Takeda, CSL Behring, Nippon Kayaku, Shionogi, Taiho, Eli Lilly, Novartis, and Mitsubishi Tanabe; personal fees and funding for clinical trials from Ono Pharmaceutical, Bayer, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, MSD, Pfizer, Taiho, and Novartis; personal fees from Celgene, Sumitomo Dainippon, Eisai, Janssen, Kyowa Kirin, Merck Serono, Otsuka, Sanofi, Takeda, Genomic Health, AbbVie, and Eli Lilly; and funding for clinical trials from AstraZeneca and Amgen outside the submitted work. K. Matsumoto reports research funds from Ono Pharmaceutical in relation to this work; grants from MSD, Chugai, Icon Japan, Eisai, Ono Pharmaceutical, AstraZeneca, and Novartis; and personal fees from MSD, Chugai, Eisai, Ono Pharmaceutical, AstraZeneca, Novartis, Eli Lilly, AbbVie, Kyowa Kirin, Centurion, and Taiho outside the submitted work. K. Yoshimura reports research funds from Ono Pharmaceutical in relation to this work; and personal fees and lecture fees from AstraZeneca, Eisai, Otsuka, Nippon Kayaku, Eli Lilly, Novartis, Boehringer Ingelheim, and Chugai outside the submitted work. S. Kitano reports research funds from Ono Pharmaceutical in relation to this work; joint research funds/contract research expenses for clinical trials from Ono Pharmaceutical, Boehringer Ingelheim, and Chugai; joint research funds from Daiichi Sankyo, Eisai, Astellas, Gilead Sciences, Takara Bio, and PACT Pharma; contract research expenses for clinical trials from Regeneron and MSD; and grants from the Japan Agency for Medical Research and Development (AMED) and Japan Society for the Promotion of Science (JSPS); consulting fees from Immunity Research; lecture fees and participation on advisory boards for Ono Pharmaceutical, AstraZeneca, Chugai, Pfizer, Boehringer Ingelheim, Novartis, Daiichi Sankyo, MSD, Sumitomo Dainippon, Eisai, Bristol-Myers Squibb, Regeneron, and GSK; lecture fees from Sanofi, Taiho, and Ayumi Pharmaceutical; participation on advisory boards for Rakuten Medical; and comment fees from Pharmaceuticals and Medical Devices Agency (PMDA) outside the submitted work. T. Takano reports research funds from Ono Pharmaceutical in relation to this work; grants provided to the institution from Chugai, Daiichi Sankyo, Ono Pharmaceutical, MSD, and Eisai; and lecture fees from Chugai, Daiichi Sankyo, Eisai, Kyowa Kirin, Pfizer, Eli Lilly, and Celltrion Healthcare outside the submitted work.
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