SynthesisFrontiers in immunology2026
Efficacy and safety of first-line immunotherapy and targeted therapy in advanced HCC: a network meta-analysis with subgroup analysis based on HBV and HCV infection.
Synthesis in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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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.
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1 citing paper in PubMed.
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4 authors.
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Abstract
Introduction: We conducted an etiology-stratified network meta-analysis of first-line systemic therapies for advanced HCC to compare newer regimens beyond sorafenib-based RCT evidence (HBV, HCV, or non-viral). Methods: Following PRISMA-NMA, we searched PubMed, Embase, Cochrane Library, and Web of Science to 01 June 2025 for first-line RCTs in advanced/unresectable HCC. Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints were objective response rate (ORR) and grade ≥3 adverse events (AEs≥3). A Bayesian fixed-effects NMA (gemtc v4.4 with rjags) reported hazard ratios (HRs) or risk ratios (RRs) with 95% credible intervals, calculated SUCRA values for ranking, and assessed network coherence using deviance information criterion differences between consistency and inconsistency models. Protocol registered in PROSPERO (CRD420251074687). Results: Twenty-four RCTs (n=13,572) evaluating 26 first-line regimens formed a connected evidence network. In the overall population, regimens with significant OS advantage over sorafenib included sintilimab plus bevacizumab biosimilar (HR = 0.57, 95% CrI 0.43-0.75), camrelizumab plus rivoceranib (HR = 0.62, 0.48-0.79), and atezolizumab plus bevacizumab (HR = 0.66, 0.51-0.84). For PFS, top-ranked combinations were camrelizumab plus rivoceranib (HR = 0.52, 0.41-0.66), anlotinib plus penpulimab (HR = 0.53, 0.41-0.68), lenvatinib plus pembrolizumab (HR = 0.55, 0.44-0.68), and sintilimab plus bevacizumab biosimilar (HR = 0.56, 0.45-0.69). ORR was highest with lenvatinib plus pembrolizumab (RR = 8.00, 4.98-12.86). Regarding safety, tislelizumab (RR = 0.42, 0.33-0.52) and nivolumab (RR = 0.45, 0.36-0.56) were associated with the lowest incidence of AEs≥3. Etiology-stratified analyses indicated that, in HBV-related HCC, sintilimab plus bevacizumab biosimilar and atezolizumab plus bevacizumab led OS rankings, with PFS favoring cabozantinib plus atezolizumab and atezolizumab plus bevacizumab. In HCV-related HCC, only atezolizumab plus bevacizumab conferred a significant OS benefit (HR = 0.43, 0.25-0.73), while PFS superiority was observed only for cabozantinib plus atezolizumab (HR = 0.73, 0.54-0.99). In non-viral HCC, the STRIDE regimen (single priming dose tremelimumab plus durvalumab) was the only regimen to significantly improve OS (HR = 0.75, 0.59-0.96). Conclusions: For first-line therapy in advanced HCC, ICI-based combinations with anti-VEGF/anti-angiogenic agents generally outperform sorafenib, with discernible etiology-specific optima: HBV-related HCC favors sintilimab plus bevacizumab biosimilar or atezolizumab plus bevacizumab; HCV-related HCC favors atezolizumab plus bevacizumab; and in non-viral disease, STRIDE demonstrates a unique OS advantage. This etiology-stratified evidence framework may guide individualized first-line decision-making, pending confirmation in head-to-head trials. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251074687, CRD420251074687.
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