Pooled Individual Patient-Data Analysis of Clinical Trials on Second-line Multikinase Inhibitors Following Immunotherapy in Hepatocellular Carcinoma.

IF 8.7 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

JHEP Reports Pub Date : 2026-09-26 DOI:10.1016/j.jhepr.2026.102043

Landon Long Chan, Hyung-Don Kim, Jaekyung Cheon, Tae Yong Kim, Hong Jae Chon, Changhoon Yoo, Stephen Lam Chan

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Abstract

Background: Three prospective clinical trials from Asia have been published on the efficacy of second-line multikinase inhibitors (MKIs) following first-line immunotherapy. We aim to study the outcomes of second-line MKIs via combined analyses of the three studies. We also aim to identify prognostic factors after immunotherapy which will inform future clinical trial design.

Methods: Individual patient-data were pooled from the three Asian clinical trials on second-line cabozantinib, lenvatinib and regorafenib. Median progression-free survival (PFS) and overall survival (OS) were computed for the overall population and those treated with first-line atezolizumab plus bevacizumab-based regimens. Prognostic factors for survival of second-line MKIs were investigated in patients treated with prior atezolizumab plus bevacizumab-based regimens.

Results: 117 patients were included in this pooled analysis. 103 patients were treated with prior atezolizumab plus bevacizumab-based regimens. Patients receiving second-line MKIs following prior first-line immunotherapy had a median PFS of 4.2 months (95%CI: 3.5-5.3 months) and OS of 10.6 months (95%CI: 9.1-15.4 months) respectively. Median PFS and OS of second-line MKIs following prior atezolizumab plus bevacizumab-based regimens were 4.2 months (95%CI: 3.5-5.3 months) and 10.6 months (95%CI: 8.9-15.4 months) respectively. Macrovascular invasion (MVI) is the only prognostic factor of OS for second-line MKIs after multivariable adjustment (HR 3.55, 95%CI 1.89-6.67, p<0.001). Previous response to immunotherapy, presence of extrahepatic spread (EHS), and baseline liver function are not associated with survival.

Conclusion: The current study provides the largest prospective data on second-line MKIs in patients with HCC who had prior first-line immunotherapy. Given the strong prognostic signal of MVI observed in this analysis, our data suggest considering MVI, rather than prior response to immunotherapy or EHS, as a stratification factor for future second-line trials.

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肝细胞癌免疫治疗后二线多激酶抑制剂临床试验的汇总个体患者数据分析。

背景：来自亚洲的三个前瞻性临床试验已经发表，研究了一线免疫治疗后二线多激酶抑制剂（MKIs）的疗效。我们的目标是通过对三项研究的综合分析来研究二线MKIs的结果。我们还旨在确定免疫治疗后的预后因素，这将为未来的临床试验设计提供信息。方法：汇总来自亚洲的三个二线药物卡博赞替尼、lenvatinib和regorafenib临床试验的个体患者数据。计算总体人群和接受一线atezolizumab加贝伐单抗治疗的患者的中位无进展生存期（PFS）和总生存期（OS）。在先前接受阿特唑单抗加贝伐单抗治疗的患者中，研究了二线MKIs的预后因素。结果：117例患者纳入本合并分析。103例患者接受了先前的阿特唑单抗加贝伐单抗方案治疗。在先前的一线免疫治疗后接受二线MKIs的患者的中位PFS为4.2个月（95%CI: 3.5-5.3个月），OS为10.6个月（95%CI: 9.1-15.4个月）。在先前的阿特唑单抗加贝伐单抗方案后，二线MKIs的中位PFS和OS分别为4.2个月（95%CI: 3.5-5.3个月）和10.6个月（95%CI: 8.9-15.4个月）。经多变量调整后，大血管侵袭（MVI）是二线MKIs OS的唯一预后因素（HR 3.55, 95%CI 1.89-6.67）。结论：本研究为既往接受过一线免疫治疗的HCC患者二线MKIs提供了最大的前瞻性数据。鉴于本分析中观察到的MVI强烈的预后信号，我们的数据建议考虑MVI，而不是先前对免疫治疗或EHS的反应，作为未来二线试验的分层因素。

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来源期刊

JHEP Reports GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

12.40

自引率

2.40%

发文量

161

审稿时长

36 days

期刊介绍： JHEP Reports is an open access journal that is affiliated with the European Association for the Study of the Liver (EASL). It serves as a companion journal to the highly respected Journal of Hepatology. The primary objective of JHEP Reports is to publish original papers and reviews that contribute to the advancement of knowledge in the field of liver diseases. The journal covers a wide range of topics, including basic, translational, and clinical research. It also focuses on global issues in hepatology, with particular emphasis on areas such as clinical trials, novel diagnostics, precision medicine and therapeutics, cancer research, cellular and molecular studies, artificial intelligence, microbiome research, epidemiology, and cutting-edge technologies. In summary, JHEP Reports is dedicated to promoting scientific discoveries and innovations in liver diseases through the publication of high-quality research papers and reviews covering various aspects of hepatology.