Hepatocellular Carcinoma · Medical · Advanced / Metastatic

CheckMate 459

Clinical question: What are the efficacy and safety outcomes in first-line nivolumab versus sorafenib?

Registry: NCT02576509 · Randomized multicentre open-label phase III trial; n=743. Evidence cut-off: 13 November 2026.

Design, population and treatment

Eligibility

Previously untreated advanced HCC.

Intervention / comparator

Nivolumab 240 mg IV q2w versus sorafenib 400 mg orally twice daily.

Design

Randomized multicentre open-label phase III trial; n=743.

Primary endpoint

OS primary.

Key efficacy outcomes

Median OS 16.4 vs 14.7 months, HR 0.85 (95% CI 0.72–1.02), p=0.075; protocol-defined significance threshold p=0.0419 not reached.

Safety and tolerability

Grade ≥3 treatment-related palmar-plantar erythrodysaesthesia <1% vs 14%, AST increase 6% vs 4%, hypertension 0 vs 7%; treatment-related deaths 4 vs 1.

Interpretation and limitations

Negative primary OS trial despite numerical OS difference and favourable toxicity profile. Not evidence of first-line OS superiority.

Median survival differences and hazard ratios must not be converted into NNT. Absolute-effect pictograms are only used when a fixed-time absolute event difference is defensibly reported.

Primary and supporting sources

Primary publication

Registry / follow-up source

Current-practice context · 13 November 2026

Historical trial findings are separated from current recommendations. Check current jurisdiction-specific guidelines, regulatory approval, liver function, biomarkers and patient factors before applying the evidence. Full guideline reconciliation and browser-rendered QA remain pending.