Integrating efficacy and safety profile in advanced HCC: A network meta-analysis of first-line systemic therapies.

Authors

Wei Yu Chua, Joseph J Zhao, Choong-Kun Lee, Yung-Yeh Su, Suat Ying Lee, Joycelyn Jie Xin Lee, David Wai-Meng Tai, Sze Huey Tan, Raghav Sundar, Kennedy Yao Yi Ng

Published in

JNCI cancer spectrum. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

Hepatocellular carcinoma(HCC) is the sixth most common cancer and the third leading cause of cancer-related death worldwide. Our updated network meta-analysis aims to compare and rank first-line treatment regimens for advanced HCC.
We searched PubMed, EMBASE, Scopus, and Cochrane from inception to May 2025 for phase III RCTs investigating first-line systemic therapies for advanced HCC. Derived hazard ratios(HRs) for each study were pooled in a random-effects NMA. The primary outcome was overall survival(OS), progression-free survival(PFS), objective response rate(ORR), and ≥ Grade 3 treatment-related adverse events(TRAE) of the assessed treatment in comparison to Sorafenib and Lenvatinib. Subgroup analysis for OS and PFS was conducted using study-level HRs. P-scores were used to rank the treatment strategies numerically.
Seventeen studies involving 12,727 patients were included in the final analysis. Nivolumab-Ipilimumab(HR:0.61,95%CI:0.44-0.84), Atezolizumab-Bevacizumab(HR:0.66,95%CI:0.48-0.90), Durvalumab-Tremelimuma(HR:0.76,95%CI:0.59-0.97), Sintilimab-BevSim(HR:0.57,95%CI:0.41-0.80), and Camrelizumab-Rivoceranib(HR:0.62,95%CI:0.45-0.85) had superior OS compared to Sorafenib. Only Sintilimab-BevSim(HR:0.66,95%CI:0.44-0.99) and Nivolumab-Ipilimumab(HR:0.70,95%CI:0.54-0.92) had superior OS compared to Lenvatinib. Based on p-score rankings only, Nivolumab-Ipilimumab had the highest p-score for OS, PFS, and ORR among the three FDA and EMA approved combination regimens, with similar ≥ Grade 3 TRAE compared to Sorafenib. In the subgroup analysis, Atezolizumab-Cabozantinib has the highest p-score for HBV, Atezolizumab-Bevacizumab the highest for HCV, Durvalumab-Tremelimumab for non-viral aetiology, and Pembrolizumab-Lenvatinib for AFP≥400.
Our NMA comprehensively compares therapeutic regimens across key clinical outcomes, including OS, PFS, ORR, and ≥ Grade 3 TRAE. The heterogeneity in treatment responses across patient subgroups underscores the importance of personalized approaches in managing HCC.

PMID:
42627365
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.

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