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)
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)
复制标题
DOI：
10.1016/j.ejca.2022.05.014
复制
发表时间：
2022-08-01
影响因子：
8.4
通讯作者：
Takano, Toshimi
中科院分区：
文献类型：
--
作者：
Ozaki, Yukinori;Tsurutani, Junji;Takano, Toshimi
背景资料：临床前模型揭示了程序性细胞死亡-1抑制剂和抗血管内皮生长因子（VEGF）抗体的潜在协同作用。因此，我们研究了使用nivolumab，贝伐单抗，紫杉醇三联疗法转移性breast cancer.Methods：这2期，多中心，单臂研究（NEWBEAT）调查的安全性和有效性的一线nivolumab，紫杉醇，贝伐单抗在人表皮生长因子受体2阴性转移性乳腺癌患者，无论程序性细胞死亡配体1的表达。主要终点为客观缓解率。关键次要终点包括无进展生存期、总生存期和毒性。一项生物标志物研究评估了肿瘤程序性细胞死亡配体1表达和血清VEGF-A水平。结果：2018年2月至2018年10月期间，57例患者入组。在39/56例患者中观察到客观缓解率（70%，95%置信区间[CI]：55.9-81.2%），符合主要终点。激素受体阳性乳腺癌患者的客观缓解率为74%，而三阴性乳腺癌患者的客观缓解率为59%。中位无进展生存期和总生存期分别为14. 0（95% CI 11. 0 - 16. 3）和32. 5（95% CI 26. 0-不可评估）个月（中位随访期：29. 5个月）。57例患者中有33例（58%）发生了3/4级药物不良反应。未发生5级不良事件。57例患者中有43例（75%）发生免疫相关不良事件，8例患者（14%）发生3/4级事件。生物标志物分析显示，肿瘤程序性细胞死亡配体1的表达与三联疗法的疗效无关。血清VEGF-高和VEGF-低groups.Conclusions：一线纳武单抗，贝伐单抗和紫杉醇治疗之间的疗效结果是相似的人表皮生长因子受体2阴性转移性乳腺癌患者显示出有前途的疗效和可控的毒性。(C)2022年，任作家。爱思唯尔有限公司出版
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. (C) 2022 The Authors. Published by Elsevier Ltd.