中国作者 | 对于全身系统治疗应答有效的晚期肝癌患者，肝切除术可带来显著的临床获益

文章摘要

阿替利珠单抗联合贝伐珠单抗治疗后行肝切除术对比维持治疗用于局部晚期肝细胞癌（TALENTOP）：一项多中心、开放标签、随机Ⅲ期试验

背景

对于接受全身系统治疗的局部晚期肝细胞癌患者，肝切除术或能带来额外获益。但是，目前尚缺乏支持该手术的高质量证据。本研究旨在探究，经全身系统治疗后产生应答的局部晚期肝细胞癌患者，肝切除术是否能够带来生存获益。

方法

这项随机、开放标签、多中心Ⅲ期试验在中国24家医院开展。研究纳入初治、存在大血管侵犯、无肝外转移的肝细胞癌患者。患者在诱导治疗阶段接受3个周期静脉注射阿替利珠单抗（1200 mg，每3周一次）联合静脉注射贝伐珠单抗（15 mg/kg体重，每3周一次），后续再加1个周期阿替利珠单抗单药治疗。完成诱导治疗后，根据实体瘤疗效评价标准1.1版（RECIST 1.1）评估达到部分缓解或疾病稳定，且被认为适合接受切除手术的患者，按1:1随机分配至两组：手术组接受肝切除术，并于术后4–6周开始接受12个月的阿替利珠单抗联合贝伐珠单抗治疗；维持治疗组继续接受阿替利珠单抗联合贝伐珠单抗治疗，直至失去临床获益或出现不可耐受毒性。随机化采用中央交互式网络应答系统，通过计算机生成的置换区组随机序列，并按肿瘤疗效和美国东部肿瘤协作组（ECOG）体能状态评分进行分层。研究为开放标签，不设盲法。主要终点为至治疗失败时间，由独立评审机构评估，并按意向治疗原则进行统计分析。至治疗失败时间定义为自随机分组起至首次记录治疗失败事件的时间。治疗失败事件包括局部复发、根据RECIST 1.1判定的疾病进展、出现肝外转移或死亡。本研究已在ClinicalTrials.gov注册（NCT04649489），试验仍在进行中。

结果

2021年4月4日至2024年7月18日期间，共有489例患者进入诱导治疗阶段。其中201例患者被随机分配至手术组（n=101；男性93例，女性8例）或维持治疗组（n=100；男性87例，女性13例）。中位随访18.4个月后，手术组的至治疗失败时间的中位数为20.4个月，维持治疗组为11.8个月（风险比0.60，95% CI 0.39–0.91；p=0.015）。手术组83例患者中有32例（39%）发生3级或4级治疗相关不良事件，维持治疗组100例患者中有21例（21%）发生此类事件。最常见的3级或4级治疗相关不良事件为丙氨酸氨基转移酶升高（手术组7例［8%］vs 维持治疗组1例［1%］）、血小板计数降低（7例［8%］vs 3例［3%］）以及蛋白尿（3例［4%］vs 7例［7%］）。手术组发生2例治疗相关死亡，死因分别为肝功能异常（考虑与阿替利珠单抗有关）和肝衰竭（考虑与阿替利珠单抗、贝伐珠单抗或手术有关）。

解释

对于存在大血管侵犯的局部晚期肝细胞癌患者，经全身系统治疗后，接受肝切除术相比单纯维持治疗，至治疗失败的时间获得延长。

END

团队介绍

本研究由复旦大学附属中山医院牵头，在中国24家医院共同开展。复旦大学附属中山医院樊嘉院士为本文的通讯作者；复旦大学附属中山医院孙惠川教授、朱小东副主任医师，以及海军军医大学第三附属医院沈锋教授为本文的共同第一作者。

Funding

Shanghai Roche Pharmaceuticals and Ministry of Science and Technology of China.

Declaration of interests

H-CS has received speaker fees from AstraZeneca, BeiGene, Eisai, Hengrui, Innovent, Merck Sharp & Dohme, Qilu Pharmaceutica, Roche, and Zelgen; and received research grants from Sino Biopharmaceutical, Eisai, Innovent, Roche, and Merck Sharp & Dohme. X-DZ has received speaker fees from AstraZeneca, BeiGene, Eisai, Hengrui, Innovent, Merck Sharp & Dohme, and Roche. JZ has received consulting fees from AstraZeneca; has received honoraria from the Asia-Pacific Primary Liver Cancer Expert Association (APPLE) and the Asian-Pacific Association for the Study of the Liver (APASL); has received travel support from the Chinese Medical Association, Beijing Dadi Medical Charity Foundation, China Zhongguancun Precision Medicine Science and Technology Foundation, Beijing Health Alliance Charitable Foundation, Beijing Medical Award Foundation, Chronic Disease Prevention and Treatment of Traditional Chinese Medicine Promotion Association, and Beijing Life Oasis Public Service Center; has served on data safety monitoring or advisory boards for AstraZeneca, Medlmmune, and Merck Sharp & Dohme; and holds leadership or fiduciary positions in boards, societies, committees, or advocacy organisations, including the Chinese Society of Oncology, the Chinese Medical Association, APPLE, the Chinese College of Surgeons, Experts Committee on Liver Cancer, Chinese Society of Clinical Oncology (CSCO), and APASL. JF has received consulting fees from AstraZeneca; has received honoraria from APPLE, the Chinese Society of Clinical Oncology, and the Chinese Anti-Cancer Association; has received travel support from CSCO, the Chinese Anti-Cancer Association, China Zhongguancun Precision Medicine Science and Technology Foundation, and Beijing Health Alliance Charitable Foundation; has served on data safety monitoring or advisory boards for AstraZeneca; and holds leadership or fiduciary positions in boards, societies, committees, or advocacy organisations, including Chinese Medical Association, the Chinese Medical Doctor Association, Chinese Society of Clinical Oncology, and the Chinese Anti-Cancer Association. All other authors declare no competing interests.

题图Copyright @ SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY

中文翻译仅供参考，所有内容以英文原文为准。

DOI:10.1016/S0140-6736(26)01252-3

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