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CheckMate 459

Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial

Phase 3N = 743NCT02576509

Population
Patients with advanced hepatocellular carcinoma not eligible for, or progressing after, surgery or locoregional treatment; no previous systemic therapy; Child-Pugh class A; ECOG performance status 0 or 1; regardless of viral hepatitis status
Design
Randomised (1:1), open-label phase 3 trial at centres in 22 countries and territories; nivolumab 240 mg intravenously every 2 weeks versus sorafenib 400 mg twice daily until progression or unacceptable toxicity, as first-line therapy. Primary endpoint overall survival in the intention-to-treat population; protocol-defined significance level p = 0.0419.
Primary endpoint
OS
Arms
  • Nivolumab (experimental, n = 371): Nivolumab 240 mg intravenously every 2 weeks
  • Sorafenib (control, n = 372): Sorafenib 400 mg orally twice daily
People
Yau T
OSHR 0.85 (95% CI 0.72–1.02)Δ median OS+1.7 months
Show the numbers
Results reported for CheckMate 459
EndpointAnalysisNivolumabSorafenibEffect
OSprimaryYau 2022median 16.4 months (13.9–18.4)median 14.7 months (11.9–17.2)HR 0.85 (95% CI 0.72–1.02)P=0.075The protocol-defined significance level of p = 0.0419 was not reached. Median follow-up for overall survival was 15.2 months (nivolumab) and 13.4 months (sorafenib); minimum follow-up 22.8 months.
Results reported for CheckMate 459
EndpointAnalysisNivolumabSorafenibEffect
OSprimaryYau 2022median 16.4 months (13.9–18.4)median 14.7 months (11.9–17.2)HR 0.85 (95% CI 0.72–1.02)P=0.075The protocol-defined significance level of p = 0.0419 was not reached. Median follow-up for overall survival was 15.2 months (nivolumab) and 13.4 months (sorafenib); minimum follow-up 22.8 months.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.850.72–1.02
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%010203040Months (modelled)
  • Nivolumab (experimental)
  • Sorafenib (control)

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

Data table (modelled values)
MonthsNivolumabSorafenib
0100.0%100.0%
1065.5%62.4%
2141.2%37.1%
3127.0%23.2%
4117.7%14.5%
Primary publication: Yau T, Park JW, Finn RS, Cheng AL, Mathurin P, Edeline J, et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022;23(1):77-90. PubMedDOI

Appears in

Sources

  1. Yau T, Park JW, Finn RS, Cheng AL, Mathurin P, Edeline J, et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022;23(1):77-90.

    PubMedDOI