SynthesisFrontiers in pharmacology2025
Comparative efficacy and safety of second-line therapies for patients with advanced hepatocellular carcinoma: a systematic review and network meta-analysis of randomized controlled trials.
Synthesis in Frontiers in pharmacology, 2025. 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
Background: The optimal second-line treatment for unresectable hepatocellular carcinoma (HCC) remains uncertain, given variability in efficacy and safety among available therapies. The comparative effectiveness and safety of second-line treatments for advanced HCC were methodically assessed in this network meta-analysis. Methods: A thorough search was conducted up until 20 February 2025, across the PubMed, Medline, Embase, Cochrane Central, and Web of Science databases to find randomized controlled trials (RCTs) evaluating second-line monotherapies (such as Ramucirumab, Regorafenib, Pembrolizumab, Cabozantinib, and Apatinib) in adults with advanced HCC. The main results comprised overall survival and progression-free survival; the supplementary results included objective response rate, disease control rate, and the occurrence of adverse events. A Bayesian random-effects network meta-analysis was employed for data synthesis, with interventions rated according to the SUCRA. Results: Eighteen RCTs involving 6,910 patients were analyzed. Ramucirumab (SUCRA: 69.2%), Regorafenib (67.6%), and Pembrolizumab (66.5%) significantly improved OS compared to control (mean difference [MD]: 2.79 months, 2.80 months, and 2.75 months, respectively). Apatinib (SUCRA: 93.0%; MD: 3.08 months), Cabozantinib (84.8%; MD: 2.65 months), and Regorafenib (48.9%; MD: 1.60 months) provided the most significant PFS benefits. Pembrolizumab (OR: 5.71, 95% CI, 2.71-12.04), Cabozantinib (OR: 5.38, 95% CI, 1.81-16.00), and Apatinib (OR: 5.32, 95% CI, 1.69-16.74) achieved superior ORR, while Apatinib, Cabozantinib, and Regorafenib had the highest DCR (OR: 3.92, 3.67, and 3.31, respectively). Pembrolizumab and Ramucirumab exhibited relatively lower incidences of severe adverse events (grade ≥3 AEs). Conclusion: Pembrolizumab and Ramucirumab had the most favorable balance of efficacy and tolerability among second-line treatments for advanced HCC and are indicated as optimal therapy alternatives to enhance clinical outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251010308.
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