经动脉化疗栓塞联合索拉非尼与单独索拉非尼治疗晚期肝细胞癌（SELECT）：一项多中心、3期、随机对照试验

IF 11.6 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver Cancer Pub Date : 2025-05-22 DOI:10.1159/000546530

Yan Zhao, Wei Bai, Rong Ding, Nan You, Lin Zheng, Lei Li, Jianbing Wu, Peng Zhang, Wukui Huang, Hui Zhang, Yongjin Zhang, Diwen Zhu, Haiping Li, Dongdong Xia, Jie Yuan, Xiaomei Li, Zhengyu Wang, Bohan Luo, Wengang Guo, Zhanxin Yin, Wei Mu, Ming Huang, Jing Li, Weixin Ren, Daiming Fan, Yong Lv, Guohong Han

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引用次数: 0

摘要

晚期肝细胞癌（HCC）患者预后极差。索拉非尼（Sorafenib）是一种多激酶抑制剂，在某些临床环境中，在免疫治疗禁忌或不可用的情况下，仍然是晚期HCC的基本治疗方法。然而，经动脉化疗栓塞（TACE）加索拉非尼的生存效益仍在研究中。方法：SELECT试验是一项在中国12个中心进行的多中心、随机、对照研究。从2013年9月7日至2019年12月4日，199例晚期HCC患者按1:1的比例随机分配接受TACE +索拉非尼或索拉非尼单药治疗。结果：研究人群的中位年龄为55岁（IQR 46-63），肝病毒感染是HCC的主要原因。在意向治疗（ITT）人群中，联合用药组和索拉非尼单药组的总生存期（OS）分析未显示有统计学差异（14.9个月[95% CI: 10.5-19.3] vs. 11.9个月[95% CI: 9.0-14.8], HR 0.862, p = 0.312）。然而，联合治疗组表现出显著改善的进展时间（TTP）(10.0个月[95% CI: 6.4-13.6] vs. 5.9个月[95% CI: 3.1-8.7]；p = 0.016)和事后无进展生存期（PFS）(8.5个月[95% CI: 6.7-10.3] vs. 5.6个月[95% CI: 4.1-7.1]；P = 0.034)。在预定义的方案分析中，联合治疗组的中位生存期明显长于单药治疗组（14.6个月[11.3-17.9]vs. 7.4个月[95% CI: 4.3-10.5], HR 0.539, p = 0.001）。结论：尽管在ITT分析中，TACE联合索拉非尼并没有显示出OS的显著改善，但它满足了次要终点，包括TTP和事后PFS。这些发现为未来试验的设计提供了有价值的见解，并强调了将局部区域干预与系统性治疗结合起来治疗晚期HCC的重要性。

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Transarterial Chemoembolization plus Sorafenib versus Sorafenib Alone in Advanced Hepatocellular Carcinoma (SELECT): A Multicenter, Phase 3, Randomized, Controlled Trial.

Introduction: Patients with advanced hepatocellular carcinoma (HCC) face an extremely poor prognosis. Sorafenib, a multikinase inhibitor, remains an essential treatment for advanced HCC in certain clinical settings where immunotherapy is either contraindicated or unavailable. However, the survival benefit of transarterial chemoembolization (TACE) plus sorafenib remains under investigation.

Methods: The SELECT trial was a multicenter, randomized, controlled study conducted across twelve centers in China. From September 7, 2013, to December 4, 2019, 199 patients with advanced-stage HCC were randomly assigned in a 1:1 ratio to receive either TACE plus sorafenib or sorafenib monotherapy.

Results: The median age of the study population was 55 years (IQR 46-63), with hepatic virus infection being the predominant cause of HCC. In the intention-to-treat (ITT) population, the overall survival (OS) analysis did not show a statistically significant difference between the combination and sorafenib monotherapy groups (14.9 months [95% CI: 10.5-19.3] vs. 11.9 months [95% CI: 9.0-14.8], HR 0.862, p = 0.312). However, the combination therapy group demonstrated significantly improved time to progression (TTP) (10.0 months [95% CI: 6.4-13.6] vs. 5.9 months [95% CI: 3.1-8.7]; p = 0.016) and post hoc progression-free survival (PFS) (8.5 months [95% CI: 6.7-10.3] vs. 5.6 months [95% CI: 4.1-7.1]; p = 0.034). In predefined per-protocol analysis, the combination therapy group showed a significantly longer median OS compared to the monotherapy group (14.6 months [11.3-17.9] vs. 7.4 months [95% CI: 4.3-10.5], HR 0.539, p = 0.001).

Conclusion: Although the combination of TACE and sorafenib did not demonstrate a significant improvement in OS in the ITT analysis, it met the secondary endpoints, including TTP and post hoc PFS. These findings provide valuable insights for the design of future trials and highlight the importance of integrating locoregional interventions with systemic therapies in the management of advanced-stage HCC.

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来源期刊

Liver Cancer Medicine-Oncology

CiteScore

20.80

自引率

7.20%

发文量

审稿时长

16 weeks

期刊介绍： Liver Cancer is a journal that serves the international community of researchers and clinicians by providing a platform for research results related to the causes, mechanisms, and therapy of liver cancer. It focuses on molecular carcinogenesis, prevention, surveillance, diagnosis, and treatment, including molecular targeted therapy. The journal publishes clinical and translational research in the field of liver cancer in both humans and experimental models. It publishes original and review articles and has an Impact Factor of 13.8. The journal is indexed and abstracted in various platforms including PubMed, PubMed Central, Web of Science, Science Citation Index, Science Citation Index Expanded, Google Scholar, DOAJ, Chemical Abstracts Service, Scopus, Embase, Pathway Studio, and WorldCat.