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晚期 HCC 免疫治疗后的二线治疗抉择☆

英文原题:Navigating second-line therapy after immunotherapy in advanced HCC☆.

PubMed 2025/10/11(内容时间) JHEP Rep Q1 · IF 8.7(JCR 2025)

研究概要

近年来,肝细胞癌的全身治疗选择显著增多,关键性 III 期试验报告了生存和缓解结局方面前所未有的改善。

中文摘要

近年来,肝细胞癌(HCC)全身治疗选择显著扩大,关键III期试验报告了前所未有的生存和应答改善。然而,这些进展主要集中于一线治疗,挑战了既有治疗顺序,也引发疾病进展后的最佳治疗方案问题。二线及后续治疗已有多种选择,包括免疫疗法、酪氨酸激酶抑制剂和局部治疗,但迄今缺乏全面头对头比较以确定理想治疗顺序。因此,指导二线治疗的大多数证据来自事后分析、真实世界数据及有限的前瞻性研究,且主要为II期设计。临床实践中,治疗决策需将不断演变的证据与患者个体因素(如既往治疗应答、肝功能和体能状态)综合考虑,同时受到监管政策和治疗可及性的限制。当前研究正评估新策略,包括疾病进展后继续免疫治疗、应用CAR-T细胞,以及靶向成纤维细胞生长因子19和Glypican-3等特定标志物的治疗。本综述总结HCC二线及后续治疗现有证据,探讨治疗排序中的关键考量,并介绍可能进一步优化治疗格局的新兴策略。

展开英文摘要原文

In recent years, systemic treatment options for hepatocellular carcinoma have expanded significantly, with pivotal phase III trials reporting unprecedented improvements in survival and response outcomes. However, these advances have largely focused on first-line strategies, challenging existing treatment sequences and raising questions about the optimal therapeutic approach following disease progression. Several therapeutic options are available in second and later lines - including immunotherapies, tyrosine kinase inhibitors, and local therapies - but so far comprehensive head-to-head comparisons to establish the ideal treatment sequence are lacking. Consequently, most evidence guiding second-line therapy has been derived from post hoc analyses, real-world data, and select prospective studies, primarily based on phase II designs. In clinical practice, treatment decisions integrate this evolving evidence base with patient-specific factors such as prior treatment response, liver function, and performance status, often within the constraints of regulatory and accessibility considerations. Ongoing research is investigating novel approaches, including the continuation of immunotherapy following progression, the application of CAR T cells, and targeted treatments against specific markers like fibroblast growth factor 19 and glypican-3. This review summarises the current evidence for second-line and subsequent therapies, explores key considerations in treatment sequencing, and highlights emerging strategies that may further refine the therapeutic landscape for hepatocellular carcinoma.

论文信息

作者
Vogel A、Saborowski A、Rimassa L、El-Khoueiry A
第一作者单位
Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.Germany
通讯作者单位
Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, Keck Medicine of USC, 1441 Eastlake Ave, Los Angeles, CA, 90022, United States.United States
文献类型
综述
期刊
JHEP reports : innovation in hepatology2026 Jan
原文标识
PubMed 41503573 · DOI 10.1016/j.jhepr.2025.101630