Integrating efficacy and safety profile in advanced HCC: A network meta-analysis of first-line systemic therapies
In brief
Nivolumab-Ipilimumab cuts death risk by 40% in advanced liver cancer
In a network meta-analysis of 17 phase III trials (12,727 patients), the nivolumab-ipilimumab combination reduced overall mortality by about 40% compared with sorafenib and performed as well as lenvatinib, while causing severe side-effects at a similar rate. It ranked highest for survival, progression-free survival and response among approved regimens, but benefits differed by viral aetiology, underscoring the need for personalized therapy.
- Journal
- JNCI cancer spectrum (Q1)
- Published
- 21 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Wei Yu Chua, Joseph J Zhao, Choong-Kun Lee, Yung-Yeh Su, Suat Ying Lee, Joycelyn Jie Xin Lee, et al.
- PMID
- 42627365
- DOI
- 10.1093/jncics/pkag084
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (top studies of the week, 23 August 2026): Network meta‑analysis of first‑line systemic HCC therapies
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.