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Bending the Curve Trial by Trial
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CELESTIAL

Cabozantinib in patients with advanced and progressing hepatocellular carcinoma

Phase 3N = 707NCT01908426

Population
Previously treated advanced hepatocellular carcinoma, Child-Pugh class A (previous sorafenib; disease progression after at least one systemic treatment; up to two previous systemic regimens for advanced disease)
Design
Randomised (2:1), double-blind phase 3 trial of cabozantinib 60 mg once daily versus matching placebo. Eligible patients had received previous sorafenib, had disease progression after at least one systemic treatment, and could have received up to two previous systemic regimens for advanced disease. Primary end point overall survival; secondary end points progression-free survival and objective response rate. Results are from the second planned interim analysis.
Primary endpoint
OS
Arms
  • Cabozantinib (experimental, n = 470): Cabozantinib 60 mg once daily
  • Placebo (control, n = 237): Matching placebo once daily
People
Abou-Alfa GK
OSHR 0.76 (95% CI 0.63–0.92)Δ median OS+2.2 monthsPFSHR 0.44 (95% CI 0.36–0.52)Δ median PFS+3.3 months
Show the numbers
Results reported for CELESTIAL
EndpointAnalysisCabozantinibPlaceboEffect
OSinterimAbou-Alfa 2018median 10.2 monthsmedian 8 monthsHR 0.76 (95% CI 0.63–0.92)P=0.005Second planned interim analysis (data cut-off 1 June 2017; 484 deaths, 78% of the 621 deaths planned for the final analysis).
PFSinterimAbou-Alfa 2018median 5.2 monthsmedian 1.9 monthsHR 0.44 (95% CI 0.36–0.52)P<0.001Secondary end point; second planned interim analysis.
ORRinterimAbou-Alfa 20184%—P=0.009Secondary end point. The abstract and full text give the placebo response rate only as less than 1% (one partial response among 237 patients), so no placebo value is recorded; cabozantinib 18 partial responses among 470 patients.
Results reported for CELESTIAL
EndpointAnalysisCabozantinibPlaceboEffect
OSinterimAbou-Alfa 2018median 10.2 monthsmedian 8 monthsHR 0.76 (95% CI 0.63–0.92)P=0.005Second planned interim analysis (data cut-off 1 June 2017; 484 deaths, 78% of the 621 deaths planned for the final analysis).
PFSinterimAbou-Alfa 2018median 5.2 monthsmedian 1.9 monthsHR 0.44 (95% CI 0.36–0.52)P<0.001Secondary end point; second planned interim analysis.
ORRinterimAbou-Alfa 20184%—P=0.009Secondary end point. The abstract and full text give the placebo response rate only as less than 1% (one partial response among 237 patients), so no placebo value is recorded; cabozantinib 18 partial responses among 470 patients.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSPFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.760.63–0.92
PFS0.440.36–0.52
Illustrative — modelled from reported values, not trial data. OS, interim.
0%25%50%75%100%0510152025Months (modelled)
  • Cabozantinib (experimental)
  • Placebo (control)

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

Data table (modelled values)
MonthsCabozantinibPlacebo
0100.0%100.0%
666.5%59.5%
1341.3%32.4%
1927.5%19.3%
2617.1%10.5%
Illustrative — modelled from reported values, not trial data. PFS, interim.
0%25%50%75%100%024681012Months (modelled)
  • Cabozantinib (experimental)
  • Placebo (control)

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

Data table (modelled values)
MonthsCabozantinibPlacebo
0100.0%100.0%
367.0%33.5%
739.3%7.8%
1026.4%2.6%
1317.7%0.9%
Primary publication: Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, Ryoo BY, et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018;379(1):54-63. PubMedDOI

Appears in

Sources

  1. Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, Ryoo BY, et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018;379(1):54-63.

    PubMedDOI