SynthesisInternational journal of clinical oncology2026
Comparative efficacy of immune checkpoint inhibitor-based regimens versus tyrosine kinase inhibitors in advanced hepatocellular carcinoma stratified by etiology: a systematic review and meta-analysis.
Synthesis in International journal of clinical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundHepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with limited treatment success in advanced stages. Tyrosine kinase inhibitors (TKIs), such as sorafenib and lenvatinib, are the first-line treatments; however, their modest survival benefits and toxicity require better alternatives. Immune checkpoint inhibitors (ICIs) have shown promise; however, direct comparisons between ICI-based regimens and TKIs, particularly those stratified by hepatocellular carcinoma (HCC) etiology, are lacking.
methodsWe conducted a systematic review and meta-analysis following PRISMA guidelines, with a protocol registered in PROSPERO (CRD420251131652). We searched the PubMed, Embase (OVID), and CENTRAL databases to compare ICI-based regimens with TKI monotherapies for advanced or unresectable HCC. Randomized controlled trials and high-quality observational studies reporting clinical outcomes (overall survival [OS], progression-free survival [PFS], objective response rate [ORR], and disease control rate [DCR]) were included. Subgroup analyses were performed for HCC etiology (hepatitis B virus (HBV) infection, hepatitis C virus (HCV), and non-viral causes) and liver function status (Child-Turcotte-Pugh [CTP] A vs. B/C). Hazard ratios (HRs) and risk ratios (RRs) were pooled using a random-effects model.
resultsSeventeen studies (randomized controlled trials and observational studies) that included patients with advanced HCC were included. ICI-based regimens significantly improved overall survival (HR = 0.81; 95% confidence interval (CI): 0.68-0.95; I
conclusionsICI-based therapies are more effective and better tolerated than are TKI monotherapies for advanced HCC, particularly in patients with HBV-related disease and preserved liver function. The efficacy appears to be attenuated in HCV-related and non-viral HCC, as well as in patients with impaired liver function, underscoring the importance of considering both disease etiology and liver functional reserve in guiding systemic treatment strategies.
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