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). (August 2022)

• Record Type: Journal Article
• Authors: Ozaki, Yukinori; Tsurutani, Junji; Mukohara, Toru; Iwasa, Tsutomu; Takahashi, Masato; Tanabe, Yuko; Kawabata, Hidetaka; Masuda, Norikazu; Futamura, Manabu; Minami, Hironobu; Matsumoto, Koji; Yoshimura, Kenichi; Kitano, Shigehisa; Takano, Toshimi
• Is Part Of: European journal of cancer. Volume 171(2022)
• Page Start: 193
• Page End: 202
• Publication Date: 2022-08
• Subjects: Nivolumab -- Bevacizumab -- Immunotherapy -- VEGF -- Metastatic breast cancer; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2022.05.014
• Languages: English
• ISSNs: 0959-8049

Abstract

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. Highlights: First clinical trial to report efficacy of nivolumab, bevacizumab, and paclitaxel. Objective response rates were promising (74% in HR+HER2− and 59% in patients with triple-negative breast cancer). The median progression-free survival and overall survival were 14.0 months and 32.5 months, respectively. Tumour programmed cell death-ligand 1 expression was not correlated with the efficacy of triple therapy. Efficacy and prognosis were similar between serum vascular endothelial growth factor-high and vascular endothelial growth factor-low groups.