What type of study is this?

This is a Human Clinical Trial study (also classified as: Meta-Analysis, Systematic Review).

What question did this study set out to answer?

This research evaluates the efficacy and safety of immunotherapeutic regimens for unresectable hepatocellular carcinoma.

December 10, 2025Open Access

Survival benefits of different immunotherapies for hepatocellular carcinoma: a meta-analysis highlighting age, gender, etiology, and tumor burden

Key Points

This research evaluates the efficacy and safety of immunotherapeutic regimens for unresectable hepatocellular carcinoma.
Conducted a meta-analysis of randomized clinical trials comparing immunotherapy and tyrosine kinase inhibitors.
Analyzed pooled hazard ratios for overall survival and progression-free survival.
Calculated odds ratios for objective response rate, disease control rate, and treatment-related adverse events.
Immunotherapy significantly improved overall survival and progression-free survival compared to tyrosine kinase inhibitors.
ICI plus targeted therapy showed the greatest benefit, with a 27% reduction in mortality and a 37% decrease in progression risk.
Subgroup analyses identified significant benefits for patients aged ≥65 years and male patients, especially with ICI plus targeted therapy.

Abstract

Background The heterogeneous efficacy of immunotherapy in hepatocellular carcinoma (HCC) remains unclear. We evaluated efficacy and safety of various immunotherapeutic regimens—including immune checkpoint inhibitor (ICI) monotherapy, dual ICIs, and ICI plus targeted therapy—for unresectable HCC, to identify patient subgroups that benefit most. Methods Randomized clinical trial evaluating immunotherapy as first-line treatment for unresectable HCC versus tyrosine kinase inhibitors (TKIs) were systematically searched. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs) were calculated. Results Twelve trials were included. Immunotherapy significantly improved OS (HR = 0.77 0.71-0.83) and PFS (HR = 0.73 0.63-0.84) versus TKIs. ICI plus targeted therapy showed the greatest benefit, reducing mortality by 27% and progression risk by 37%. Subgroup analyses revealed patients aged ≥65 years and male patients derived substantial OS and PFS benefits, particularly from ICI plus targeted therapy, whereas younger patients (65 years) benefited more from dual ICIs. Additional favorable subgroups included Asian patients, HBV-positive patients, those with poor performance status, macrovascular invasion and/or extrahepatic spread, and Barcelona Clinic Liver Cancer stage C. Notably, female patients showed no significant OS improvement across any regimen. Moreover, non-Asian patients, those with hepatitis C, BCLC stage B, or AFP 400 ng/mL derived limited immunotherapy benefit across regimens. Conclusions Immunotherapy improves survival in unresectable HCC, with differential subgroup benefits highlighting the necessity for personalized strategies. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ , identifier CRD42025635108.

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