Finn, Richard SRichard SFinnGu, KangshengKangshengGuChen, XiXiChenMerle, PhilippePhilippeMerleLee, Kyung-HunKyung-HunLeeBouattour, MohamedMohamedBouattourCao, PeiguoPeiguoCaoWang, WeiWeiWangANN-LII CHENGZhu, LiangjunLiangjunZhuLim, Ho YeongHo YeongLimKudo, MasatoshiMasatoshiKudoPan, YueyinYueyinPanChang, Ting-TsungTing-TsungChangEdeline, JulienJulienEdelineLi, WeiWeiLiYang, PingPingYangLi, ChenChenLiLi, JianfengJianfengLiSiegel, Abby BAbby BSiegelQin, ShukuiShukuiQin2025-09-052025-09-052025-06https://scholars.lib.ntu.edu.tw/handle/123456789/731867We 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).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.In total, 578 and 288 participants who received pembrolizumab and placebo, respectively, were included in this analysis. Compared with placebo, pembrolizumab improved overall survival (hazard ratio 0.79, 95% CI 0.67-0.93), progression-free survival (per RECIST v1.1 by blinded independent central review [BICR]; hazard ratio 0.76, 95% CI 0.64-0.89), and objective response rate (per RECIST v1.1 by BICR; 15.4% 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.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 pembrolizumab as second-line therapy for advanced HCC after prior sorafenib- or oxaliplatin-based therapy.To obtain a more precise estimate of the pembrolizumab treatment effect in participants with previously treated advanced hepatocellular carcinoma, we performed a meta-analysis of efficacy using pooled participant data from the phase III KEYNOTE-240 and KEYNOTE-394 studies. Subgroup analyses showed that the treatment effect of pembrolizumab was generally similar across baseline characteristics, including viral status, Barcelona Clinic Liver Cancer stage, and geographic region. This meta-analysis provides further evidence of the global benefit of pembrolizumab as second-line therapy for advanced hepatocellular carcinoma.Registered at ClinicalTrials.gov NCT02702401 (KEYNOTE-240) and NCT03062358 (KEYNOTE-394).enGlobalPooledPost hocProgrammed cell death ligand 1Randomized[SDGs]SDG3journal article10.1016/j.jhepr.2025.10135040486134