Benmelstobart、安罗替尼和化疗治疗广泛期小细胞肺癌：一项随机 3 期试验。
Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.
发表日期：2024 Jul 11
作者：
Ying Cheng, Jianhua Chen, Wei Zhang, Chao Xie, Qun Hu, Ningning Zhou, Chun Huang, Shihong Wei, Hong Sun, Xingya Li, Yan Yu, Jinhuo Lai, Huaping Yang, Haohui Fang, Hualin Chen, Peng Zhang, Kangsheng Gu, Qiming Wang, Jianhua Shi, Tienan Yi, Xingxiang Xu, Xianwei Ye, Daqing Wang, Conghua Xie, Chunling Liu, Yulong Zheng, Daren Lin, Wu Zhuang, Ping Lu, Guohua Yu, Jinzhang Li, Yuhai Gu, Baolan Li, Rong Wu, Ou Jiang, Zaiyi Wang, Guowu Wu, Haifeng Lin, Diansheng Zhong, Yanhua Xu, Yongqian Shu, Di Wu, Xingwu Chen, Jie Wang, Minghui Wang, Runxiang Yang
来源：
NATURE MEDICINE
摘要：
免疫化疗是广泛期小细胞肺癌（ES-SCLC）的一线标准疗法。该方案与抗血管生成药物相结合可能会提高疗效。 ETER701 是一项多中心、双盲、随机、安慰剂对照 3 期试验，研究 Benmeltobart（一种新型程序性死亡配体 1 (PD-L1) 抑制剂）与安罗替尼（一种多靶点抗血管生成药物）的有效性和安全性小分子）和标准化疗治疗初治 ES-SCLC。 ETER701 试验评估了两个主要终点：独立审查委员会根据 RECIST 1.1 评估的无进展生存期和总生存期 (OS)。这里报告了预先指定的最终无进展生存期和中期 OS 分析。患者随机接受苯美斯托巴特和安罗替尼加依托泊苷/卡铂（EC；n = 246）、安慰剂和安罗替尼加EC（n = 245）或双安慰剂加EC（“单独EC”；n = 247），然后接受匹配的维持治疗。与单独使用 EC 相比，贝梅尔斯托巴特和安罗替尼加 EC 组的中位 OS 延长（19.3 个月与 11.9 个月；风险比 0.61；P=0.0002），而安罗替尼加 EC 组的 OS 改善没有统计学意义（13.3 个月与 11.9 个月；风险比） 0.86；P = 0.1723)。 Benmeltobart 组和安罗替尼加 EC 组、安罗替尼加 EC 组和单独 EC 组中 3 级或以上治疗相关不良事件的发生率分别为 93.1%、94.3% 和 87.0%。这项免疫化疗加多靶点抗血管生成作为一线治疗的研究取得的中位 OS 高于之前 ES-SCLC 患者随机研究中记录的中位 OS。安全状况被评估为可容忍且可管理。我们的研究结果表明，在免疫化疗的基础上添加抗血管生成治疗可能是治疗 ES-SCLC 的一种有效且安全的方法。 ClinicalTrials.gov 标识符：NCT04234607 .© 2024。作者。
Immunochemotherapy is the first-line standard for extensive-stage small-cell lung cancer (ES-SCLC). Combining the regimen with anti-angiogenesis may improve efficacy. ETER701 was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial that investigated the efficacy and safety of benmelstobart (a novel programmed death-ligand 1 (PD-L1) inhibitor) with anlotinib (a multi-target anti-angiogenic small molecule) and standard chemotherapy in treatment-naive ES-SCLC. The ETER701 trial assessed two primary endpoints: Independent Review Committee-assessed progression-free survival per RECIST 1.1 and overall survival (OS). Here the prespecified final progression-free survival and interim OS analysis is reported. Patients randomly received benmelstobart and anlotinib plus etoposide/carboplatin (EC; n = 246), placebo and anlotinib plus EC (n = 245) or double placebo plus EC ('EC alone'; n = 247), followed by matching maintenance therapy. Compared with EC alone, median OS was prolonged with benmelstobart and anlotinib plus EC (19.3 versus 11.9 months; hazard ratio 0.61; P = 0.0002), while improvement of OS was not statistically significant with anlotinib plus EC (13.3 versus 11.9 months; hazard ratio 0.86; P = 0.1723). The incidence of grade 3 or higher treatment-related adverse events was 93.1%, 94.3% and 87.0% in the benmelstobart and anlotinib plus EC, anlotinib plus EC, and EC alone groups, respectively. This study of immunochemotherapy plus multi-target anti-angiogenesis as first-line treatment achieved a median OS greater than recorded in prior randomized studies in patients with ES-SCLC. The safety profile was assessed as tolerable and manageable. Our findings suggest that the addition of anti-angiogenesis therapy to immunochemotherapy may represent an efficacious and safe approach to the management of ES-SCLC. ClinicalTrials.gov identifier: NCT04234607 .© 2024. The Author(s).