一线苯美司托巴特联合安罗替尼对比舒尼替尼治疗晚期肾细胞癌（ETER100）：一项多中心、随机、开放标签的3期试验
First-line benmelstobart plus anlotinib versus sunitinib in advanced renal cell carcinoma (ETER100): a multicentre, randomised, open-label, phase 3 trial.
作者信息
Zhou Aiping, Shen Pengfei, Li Juan, Qu Wang, Wang Zengjun, Ren Xiubao, Li Yuan, Jiang Shusuan, Li Gang, Zeng Yu, Qin Weijun, Wu Jin, Chen Peng, Zhou Fangjian, Guo Hongqian, Ji Zhigang, Wang Yongquan, He Zhisong, Wu Jitao, Shi Benkang, Liu Lian, Yao Xudong, Ma Lulin, Liu Ziling, Gou Xin, Fu Bin, Wang Shaogang, Jiang Kui, Chong Tie, Tu Xinhua, Zhang Xu, Yu Dexin, Rexiati Mulati, Xue Xueyi, Fei Jing, Wan Jianghou, Jia Liqun, He Yi, Cui Tongjian, Yang An-Qi, Guo Jun, Sheng Xinan
机构信息
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
出版信息
Lancet Oncol. 2025 Sep;26(9):1145-1157. doi: 10.1016/S1470-2045(25)00343-2.
BACKGROUND
The underexplored potential of PD-L1 blockade in advanced renal cell carcinoma highlights an urgent need for novel agents. This trial aimed to compare benmelstobart (a novel PD-L1 inhibitor) plus anlotinib with sunitinib as first-line treatment for advanced renal cell carcinoma.
METHODS
ETER100 was a multicentre, randomised, open-label, phase 3 trial conducted at 37 medical sites in China. We included patients aged 18-80 years, who had previously untreated, advanced, clear-cell renal cell carcinoma, and an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned (1:1) patients to receive either benmelstobart (intravenous, 1200 mg, once every 3 weeks) plus anlotinib (oral, 12 mg, once daily for the first 2 weeks of a 3-week cycle) or sunitinib (oral, 50 mg, once daily for the first 4 weeks of a 6-week cycle) until disease progression, unacceptable toxicity, investigator's decision, or patient withdrawal. Randomisation was done centrally with stratified block randomisation (block size 4) and stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk. The primary endpoint was progression-free survival as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumours version 1.1 in the full analysis set (ie, randomly assigned patients who received at least one dose of study drug without the violation of key inclusion criteria) and per-protocol set (ie, randomly assigned patients who received at least one cycle of protocol treatment without major protocol violations and had at least one efficacy assessment). In this Article, we report the results of a prespecified interim analysis. This ongoing study, closed to recruitment, is registered with ClinicalTrials.gov, NCT04523272.
FINDINGS
Between Aug 25, 2020, and Feb 6, 2023, we assessed 687 patients for eligibility, 531 (77%) of whom were randomly assigned to receive either benmelstobart plus anlotinib (266 [50%] patients) or sunitinib (265 [50%] patients). 527 (99%) patients were included in the full analysis set (263 [50%] patients who received benmelstobart plus anlotinib and 264 [50%] who received sunitinib). All patients were Chinese (400 [76%] men and 127 [24%] women), with a median age of 60 years (IQR 54-67). As of the cutoff date (Jan 31, 2024), the median follow-up was 22·8 months (IQR 15·2-29·7). In the full analysis set, median progression-free survival was significantly longer with benmelstobart plus anlotinib than with sunitinib (19·0 months [95% CI 15·3-22·8] vs 9·8 months [8·4-12·4]; hazard ratio [HR] 0·53 [95% CI 0·42-0·67]; p<0·0001). In the per-protocol set, median progression-free survival was 19·0 months (16·5-22·8) in the benmelstobart-anlotinib group versus 11·0 months (8·5-13·6) in the sunitinib group (HR 0·55 [0·43-0·70]; p<0·0001). The most common grade 3 or worse treatment-related adverse event was hypertension (occurring in 91 [34%] of 264 patients in the benmelstobart-anlotinib group vs 55 [21%] of 264 in the sunitinib group). Serious treatment-related adverse events occurred in 63 (24%) patients in the benmelstobart-anlotinib group and in 42 (16%) patients in the sunitinib group. In the benmelstobart-anlotinib group, three (1%) deaths occurred due to treatment-related adverse events (one each with cardiac-respiratory arrest, unknown reason, and renal failure) and no deaths occurred in the sunitinib group.
INTERPRETATION
Benmelstobart plus anlotinib improved progression-free survival compared with sunitinib among patients with previously untreated, advanced clear-cell renal cell carcinoma. These findings suggest the potential of benmelstobart plus anlotinib as a treatment option for this population.
FUNDING
Chia Tai Tianqing Pharmaceutical Group and CSCO Clinical Oncology Research Foundation.
TRANSLATION
For the Chinese translation of the abstract see Supplementary Materials section.
背景
程序性死亡受体 1 配体（PD-L1）阻断疗法在晚期肾细胞癌中尚未得到充分探索的潜力凸显了对新型药物的迫切需求。本试验旨在比较苯美司托巴特（一种新型 PD-L1 抑制剂）联合安罗替尼与舒尼替尼作为晚期肾细胞癌一线治疗方案的疗效。
方法
ETER100 是一项在中国 37 个医学中心进行的多中心、随机、开放标签的 3 期试验。我们纳入了年龄在 18 - 80 岁之间、先前未经治疗的晚期透明细胞肾细胞癌患者，且东部肿瘤协作组体能状态评分为 0 或 1。我们将患者按 1:1 随机分配，分别接受苯美司托巴特（静脉注射，1200 mg，每 3 周一次）联合安罗替尼（口服，12 mg，在 3 周周期的前 2 周每日一次）或舒尼替尼（口服，50 mg，在 6 周周期的前 4 周每日一次），直至疾病进展、出现不可接受的毒性、研究者做出决定或患者退出。随机分组在中心进行，采用分层区组随机化（区组大小为 4），并根据国际转移性肾细胞癌数据库联盟风险进行分层。主要终点是根据实体瘤疗效评价标准第 1.1 版，由盲法独立中央审查评估的无进展生存期。在全分析集（即随机分配且接受至少一剂研究药物且未违反关键纳入标准的患者）和符合方案集（即随机分配且接受至少一个周期方案治疗且未发生重大方案违反且至少有一次疗效评估的患者）中进行评估。在本文中，我们报告了预先指定的中期分析结果。这项正在进行的研究已停止招募患者，已在 ClinicalTrials.gov 注册，注册号为 NCT04523272。
结果
在 2020 年 8 月 25 日至 2023 年 2 月 6 日期间，我们评估了 687 例患者的 eligibility（此处原文可能有误，推测为 eligibility），其中 531 例（77%）被随机分配接受苯美司托巴特联合安罗替尼（266 例[50%]患者）或舒尼替尼（265 例[50%]患者）。527 例（99%）患者被纳入全分析集（263 例[50%]接受苯美司托巴特联合安罗替尼的患者和 264 例[50%]接受舒尼替尼的患者）。所有患者均为中国人（400 例[76%]男性和 127 例[24%]女性），中位年龄为 60 岁（四分位间距 54 - 67）。截至截止日期（2024 年 1 月 31 日），中位随访时间为 22.8 个月（四分位间距 15.2 - 29.7）。在全分析集中，苯美司托巴特联合安罗替尼组的中位无进展生存期显著长于舒尼替尼组（19.0 个月[95%置信区间 15.3 - 22.8] vs 9.8 个月[8.4 - 12.4]；风险比[HR] 0.53 [95%置信区间 0.42 - 0.67]；p < 0.0001）。在符合方案集中，苯美司托巴特 - 安罗替尼组的中位无进展生存期为 19.0 个月（16.5 - 22.8），而舒尼替尼组为 11.0 个月（8.5 - 13.6）（HR 0.55 [0.43 - 0.70]；p < 0.0001）。最常见的 3 级或更严重的治疗相关不良事件是高血压（苯美司托巴特 - 安罗替尼组 264 例患者中有 91 例[34%]发生，舒尼替尼组 264 例患者中有 55 例[21%]发生）。苯美司托巴特 - 安罗替尼组有 63 例（24%）患者发生严重治疗相关不良事件，舒尼替尼组有 42 例（16%）患者发生。在苯美司托巴特 - 安罗替尼组，有 3 例（1%）患者因治疗相关不良事件死亡（分别为心搏呼吸骤停、原因不明和肾衰竭各 1 例），舒尼替尼组无死亡病例。
解读
与舒尼替尼相比，苯美司托巴特联合安罗替尼在先前未经治疗的晚期透明细胞肾细胞癌患者中改善了无进展生存期。这些发现表明苯美司托巴特联合安罗替尼作为该人群治疗选择的潜力。
资助
正大天晴药业集团和中国临床肿瘤学会（CSCO）临床肿瘤学研究基金会。
中文摘要的翻译见补充材料部分。
Zotero 插件