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Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial.

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Omuro, A; Brandes, AA; Carpentier, AF; Idbaih, A; Reardon, DA; Cloughesy, T; Sumrall, A; Baehring, J; van den Bent, M; Bähr, O; Lombardi, G ...
Published in: Neuro Oncol
January 5, 2023

BACKGROUND: Addition of temozolomide (TMZ) to radiotherapy (RT) improves overall survival (OS) in patients with glioblastoma (GBM), but previous studies suggest that patients with tumors harboring an unmethylated MGMT promoter derive minimal benefit. The aim of this open-label, phase III CheckMate 498 study was to evaluate the efficacy of nivolumab (NIVO) + RT compared with TMZ + RT in newly diagnosed GBM with unmethylated MGMT promoter. METHODS: Patients were randomized 1:1 to standard RT (60 Gy) + NIVO (240 mg every 2 weeks for eight cycles, then 480 mg every 4 weeks) or RT + TMZ (75 mg/m2 daily during RT and 150-200 mg/m2/day 5/28 days during maintenance). The primary endpoint was OS. RESULTS: A total of 560 patients were randomized, 280 to each arm. Median OS (mOS) was 13.4 months (95% CI, 12.6 to 14.3) with NIVO + RT and 14.9 months (95% CI, 13.3 to 16.1) with TMZ + RT (hazard ratio [HR], 1.31; 95% CI, 1.09 to 1.58; P = .0037). Median progression-free survival was 6.0 months (95% CI, 5.7 to 6.2) with NIVO + RT and 6.2 months (95% CI, 5.9 to 6.7) with TMZ + RT (HR, 1.38; 95% CI, 1.15 to 1.65). Response rates were 7.8% (9/116) with NIVO + RT and 7.2% (8/111) with TMZ + RT; grade 3/4 treatment-related adverse event (TRAE) rates were 21.9% and 25.1%, and any-grade serious TRAE rates were 17.3% and 7.6%, respectively. CONCLUSIONS: The study did not meet the primary endpoint of improved OS; TMZ + RT demonstrated a longer mOS than NIVO + RT. No new safety signals were detected with NIVO in this study. The difference between the study treatment arms is consistent with the use of TMZ + RT as the standard of care for GBM.ClinicalTrials.gov NCT02617589.

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Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

January 5, 2023

Volume

25

Issue

1

Start / End Page

123 / 134

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Temozolomide
  • Progression-Free Survival
  • Oncology & Carcinogenesis
  • Nivolumab
  • Humans
  • Glioblastoma
  • Disease-Free Survival
  • DNA Repair Enzymes
  • DNA Modification Methylases
 

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Omuro, A., Brandes, A. A., Carpentier, A. F., Idbaih, A., Reardon, D. A., Cloughesy, T., … Weller, M. (2023). Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. Neuro Oncol, 25(1), 123–134. https://doi.org/10.1093/neuonc/noac099
Omuro, Antonio, Alba A. Brandes, Antoine F. Carpentier, Ahmed Idbaih, David A. Reardon, Timothy Cloughesy, Ashley Sumrall, et al. “Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial.Neuro Oncol 25, no. 1 (January 5, 2023): 123–34. https://doi.org/10.1093/neuonc/noac099.
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 Jan 5;25(1):123–34.
Omuro, Antonio, et al. “Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial.Neuro Oncol, vol. 25, no. 1, Jan. 2023, pp. 123–34. Pubmed, doi:10.1093/neuonc/noac099.
Omuro A, Brandes AA, Carpentier AF, Idbaih A, Reardon DA, Cloughesy T, Sumrall A, Baehring J, van den Bent M, Bähr O, Lombardi G, Mulholland P, Tabatabai G, Lassen U, Sepulveda JM, Khasraw M, Vauleon E, Muragaki Y, Di Giacomo AM, Butowski N, Roth P, Qian X, Fu AZ, Liu Y, Potter V, Chalamandaris A-G, Tatsuoka K, Lim M, Weller M. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. Neuro Oncol. 2023 Jan 5;25(1):123–134.
Journal cover image

Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

January 5, 2023

Volume

25

Issue

1

Start / End Page

123 / 134

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Temozolomide
  • Progression-Free Survival
  • Oncology & Carcinogenesis
  • Nivolumab
  • Humans
  • Glioblastoma
  • Disease-Free Survival
  • DNA Repair Enzymes
  • DNA Modification Methylases