ArticleJHEP reports : innovation in hepatology2025
Second-line pembrolizumab for advanced HCC: Meta-analysis of the phase III KEYNOTE-240 and KEYNOTE-394 studies.
Article in JHEP reports : innovation in hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 7 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase III Study of Pembrolizumab (MK-3475) vs. Best Supportive Care as Second-Line Therapy in Subjects With Previously Systemically Treated Advanced Hepatocellular Carcinoma (KEYNOTE-240)
A Phase III Randomized Double-blind Study of Pembrolizumab Plus Best Supportive Care vs. Placebo Plus Best Supportive Care as Second-Line Therapy in Asian Subjects With Previously Systemically Treated Advanced Hepatocellular Carcinoma (KEYNOTE-394)
Who cites it
7 citing papers in PubMed.
- Systemic treatment paradigms for unresectable and advanced hepatocellular carcinoma in Europe.The Lancet regional health. Europe · 2026Review
- Trial design and end points in hepatocellular carcinoma: an EASL-AASLD-ILCA consensus statement.Nature reviews. Clinical oncology · 2026Article
- T Cell Exhaustion in Hepatocellular Carcinoma: A Substantial Barrier in Immunotherapy.Journal of cellular and molecular medicine · 2026Review
- Metabolic dysfunction-associated steatotic liver disease, insulin resistance and hepatocellular carcinoma: A deadly triad.European journal of clinical investigation · 2026Review
- The Triad of NF-κB, HIF-1α, and Oxidative Stress in Hepatocellular Carcinoma: Pathogenesis, Clinical Challenges, and Therapeutic Potential of CIGB-552 in Liver Transplantation.International journal of biological sciences · 2026Review
- Cost-effectiveness analysis of anlotinib plus penpulimab versus sorafenib in the treatment of unresectable hepatocellular carcinoma.Human vaccines & immunotherapeutics · 2025Article
- Combined Immunotherapy in Treating Patients with Advanced Hepatocellular Carcinoma.Biomedicines · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors.
Funding
Abstract
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: 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% 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 pembrolizumab as second-line therapy for advanced HCC after prior sorafenib- or oxaliplatin-based therapy. Impact and implications: 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. Clinical Trials Registration: Registered at ClinicalTrials.gov NCT02702401 (KEYNOTE-240) and NCT03062358 (KEYNOTE-394).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.