Second-line pembrolizumab for advanced HCC: Meta-analysis of the phase III KEYNOTE-240 and KEYNOTE-394 studies

作者：Richard S. Finn, Kangsheng Gu, Xi Chen, Philippe Merle, Kyung-Hun Lee, Mohamed Bouattour, Peiguo Cao, Wei Wang, Ann‐Lii Cheng, Liangjun Zhu, Ho Yeong Lim, Masatoshi Kudo, Yueyin Pan, Ting‐Tsung Chang, Julien Edeline, Wei Li, Ping Yang, Chen Li, Jianfeng Li, Abby B. Siegel, Shukui Qin · 发表于：JHEP Reports · 年份：2025 · DOI：10.1016/j.jhepr.2025.101350 · 被引用次数：10 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cancer Immunotherapy and Biomarkers、Cancer Mechanisms and Therapy

Background & Aims: We performed a meta-analysis of data from the KEYNOTE-240 and KEYNOTE-394 studies to obtain a more precise estimate of the pembrolizumab treatment effect in participants with previously treated advanced hepatocellular carcinoma (HCC). Methods: Participants with confirmed HCC and disease progression after treatment with or intolerance of sorafenib or oxaliplatin-based chemotherapy (KEYNOTE-394 only), Barcelona Clinic Liver Cancer stage C or B disease not amenable to or refractory to locoregional therapy, and one or more measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were randomly assigned 2:1 to receive pembrolizumab or placebo for ≤35 cycles. Data from the KEYNOTE-240 and KEYNOTE-394 intention-to-treat populations were pooled, and the treatment effect was evaluated for pembrolizumab and placebo separately. Results: 2.8%, for an estimated treatment difference of 12.5%; 95% CI 8.8-16.2). Subgroup analyses showed that the treatment effect of pembrolizumab was generally similar across baseline participant characteristics, including viral status, Barcelona Clinic Liver Cancer stage, and geographic region. Conclusions: Meta-analysis of KEYNOTE-240 and KEYNOTE-394 showed that pembrolizumab provides clinically meaningful improvement in overall survival, progression-free survival, and objective response rate. This analysis expands on findings from each study individually and provides further evidence of the global benefit of ...