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Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial

Phase 3N = 954NCT01761266

Population
Patients with unresectable hepatocellular carcinoma who had not received treatment for advanced disease; 1492 recruited, 954 eligible patients randomised
Design
Open-label, multicentre phase 3 non-inferiority trial at 154 sites in 20 countries; randomisation 1:1 to lenvatinib (12 mg/day if bodyweight 60 kg or more, 8 mg/day if under 60 kg) or sorafenib 400 mg twice daily in 28-day cycles; primary endpoint overall survival, non-inferiority margin 1.08; efficacy analysis by intention to treat.
Primary endpoint
OS
Arms
  • Lenvatinib (experimental, n = 478): Lenvatinib 12 mg/day (bodyweight 60 kg or more) or 8 mg/day (under 60 kg)
  • Sorafenib (control, n = 476): Sorafenib 400 mg twice daily
People
Kudo M
OSHR 0.92 (95% CI 0.79–1.06)Δ median OS+1.3 months
Show the numbers
Results reported for Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial
EndpointAnalysisLenvatinibSorafenibEffect
OSprimaryKudo 2018median 13.6 months (12.1–14.9)median 12.3 months (10.4–13.9)HR 0.92 (95% CI 0.79–1.06)Meets the non-inferiority criterion (margin 1.08); the abstract reports no superiority test or p-value.
Results reported for Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial
EndpointAnalysisLenvatinibSorafenibEffect
OSprimaryKudo 2018median 13.6 months (12.1–14.9)median 12.3 months (10.4–13.9)HR 0.92 (95% CI 0.79–1.06)Meets the non-inferiority criterion (margin 1.08); the abstract reports no superiority test or p-value.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.920.79–1.06
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%051015202530Months (modelled)
  • Lenvatinib (experimental)
  • Sorafenib (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsLenvatinibSorafenib
0100.0%100.0%
963.2%60.2%
1742.0%38.4%
2626.6%23.1%
3417.7%14.7%
Primary publication: Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163-1173. PubMedDOI

Appears in

Sources

  1. Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163-1173.

    PubMedDOI