Skip to content
Bending the Curve Trial by Trial
?

CheckMate 498

Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter (CheckMate 498)

Phase 3N = 560NCT02617589

Population
Patients with newly diagnosed glioblastoma with unmethylated MGMT promoter; 560 randomised, 280 to each arm
Design
Open-label randomised phase 3 trial (1:1) of standard radiotherapy (60 Gy) plus nivolumab (240 mg every 2 weeks for eight cycles, then 480 mg every 4 weeks) versus radiotherapy plus temozolomide (75 mg/m2 daily during radiotherapy, then 150-200 mg/m2/day on 5 of 28 days during maintenance); primary endpoint overall survival
Primary endpoint
OS
Arms
  • Nivolumab plus radiotherapy (experimental, n = 280): Radiotherapy 60 Gy plus nivolumab 240 mg every 2 weeks for eight cycles, then 480 mg every 4 weeks
  • Temozolomide plus radiotherapy (control, n = 280): Radiotherapy 60 Gy plus temozolomide 75 mg/m2 daily during radiotherapy, then 150-200 mg/m2/day on 5 of 28 days
People
Omuro A
OSHR 1.31 (95% CI 1.09–1.58)Δ median OS−1.5 monthsPFSHR 1.38 (95% CI 1.15–1.65)Δ median PFS−0.2 months
Show the numbers
Results reported for CheckMate 498
EndpointAnalysisNivolumab plus radiotherapyTemozolomide plus radiotherapyEffect
OSRandomised patients (n=560); analysis population not stated in the abstractOverall survival (primary endpoint)primaryOmuro 2023median 13.4 months (12.6–14.3)median 14.9 months (13.3–16.1)HR 1.31 (95% CI 1.09–1.58)P=.0037The abstract states the study did not meet the primary endpoint and that temozolomide plus radiotherapy showed a longer median overall survival.
PFSRandomised patients (n=560); analysis population not stated in the abstractProgression-free survivalprimaryOmuro 2023median 6 months (5.7–6.2)median 6.2 months (5.9–6.7)HR 1.38 (95% CI 1.15–1.65)
Results reported for CheckMate 498
EndpointAnalysisNivolumab plus radiotherapyTemozolomide plus radiotherapyEffect
OSRandomised patients (n=560); analysis population not stated in the abstractOverall survival (primary endpoint)primaryOmuro 2023median 13.4 months (12.6–14.3)median 14.9 months (13.3–16.1)HR 1.31 (95% CI 1.09–1.58)P=.0037The abstract states the study did not meet the primary endpoint and that temozolomide plus radiotherapy showed a longer median overall survival.
PFSRandomised patients (n=560); analysis population not stated in the abstractProgression-free survivalprimaryOmuro 2023median 6 months (5.7–6.2)median 6.2 months (5.9–6.7)HR 1.38 (95% CI 1.15–1.65)
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSPFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS1.311.09–1.58
PFS1.381.15–1.65
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%0102030Months (modelled)
  • Nivolumab plus radiotherapy (experimental)
  • Temozolomide plus radiotherapy (control)

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

Data table (modelled values)
MonthsNivolumab plus radiotherapyTemozolomide plus radiotherapy
0100.0%100.0%
962.8%65.8%
1937.4%41.3%
2823.5%27.2%
3714.8%17.9%
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%02468101214Months (modelled)
  • Nivolumab plus radiotherapy (experimental)
  • Temozolomide plus radiotherapy (control)

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

Data table (modelled values)
MonthsNivolumab plus radiotherapyTemozolomide plus radiotherapy
0100.0%100.0%
463.0%63.9%
839.7%40.9%
1225.0%26.1%
1615.7%16.7%
Primary publication: Omuro A, Brandes AA, Carpentier AF, Idbaih A, Reardon DA, Cloughesy T, et al. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. Neuro Oncol. 2023;25(1):123-134. PubMedDOI

Appears in

Sources

  1. Omuro A, Brandes AA, Carpentier AF, Idbaih A, Reardon DA, Cloughesy T, et al. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. Neuro Oncol. 2023;25(1):123-134.

    PubMedDOI