Hepatocellular Carcinoma · Medical · Advanced / Metastatic

EVOLVE-1

Clinical question: What are the efficacy and safety outcomes in second-line after sorafenib progression/intolerance?

Registry: NCT01035229 · Phase III randomized double-blind placebo-controlled trial; n=546. Evidence cut-off: 13 November 2026.

Design, population and treatment

Eligibility

Advanced HCC progressing during/after or intolerant of sorafenib.

Intervention / comparator

Everolimus 7.5 mg orally daily versus placebo, with best supportive care.

Design

Phase III randomized double-blind placebo-controlled trial; n=546.

Primary endpoint

OS primary; time to progression and disease control secondary.

Key efficacy outcomes

Median OS 7.6 vs 7.3 months, HR 1.05 (95% CI 0.86–1.27), p=0.68. Time to progression 3.0 vs 2.6 months, HR 0.93.

Safety and tolerability

Grade 3/4 anaemia 7.8% vs 3.3%, asthenia 7.8% vs 5.5%, decreased appetite 6.1% vs 0.5%; HBV reactivation occurred.

Interpretation and limitations

Negative phase III study; everolimus did not improve OS after sorafenib. Historical negative evidence.

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.