Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter

Michael Lim, Michael Weller, Ahmed Idbaih, Joachim Steinbach, Gaetano Finocchiaro, Raju R. Raval, George Ansstas, Joachim Baehring, Jennie W. Taylor, Jerome Honnorat, Kevin Petrecca, Filip De Vos, Antje Wick, Ashley Sumrall, Solmaz Sahebjam, Ingo K. Mellinghoff, Masashi Kinoshita, Mustimbo Roberts, Ruta Slepetis, Deepti WaradDavid Leung, Michelle Lee, David A. Reardon, Antonio Omuro

Research output: Contribution to journalArticlepeer-review

184 Scopus citations

Abstract

Background: Nearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase III randomized CheckMate 548 study was to evaluate RT + TMZ combined with the immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in patients with newly diagnosed glioblastoma with methylated MGMT promoter (NCT02667587). Methods: Patients (N = 716) were randomized 1:1 to NIVO [(240 mg every 2 weeks × 8, then 480 mg every 4 weeks) + RT (60 Gy over 6 weeks) + TMZ (75 mg/m2 once daily during RT, then 150-200 mg/m2 once daily on days 1-5 of every 28-day cycle × 6)] or PBO + RT + TMZ following the same regimen. The primary endpoints were progression-free survival (PFS) and overall survival (OS) in patients without baseline corticosteroids and in all randomized patients. Results: As of December 22, 2020, median (m)PFS (blinded independent central review) was 10.6 months (95% CI, 8.9-11.8) with NIVO + RT + TMZ vs 10.3 months (95% CI, 9.7-12.5) with PBO + RT + TMZ (HR, 1.1; 95% CI, 0.9-1.3) and mOS was 28.9 months (95% CI, 24.4-31.6) vs 32.1 months (95% CI, 29.4-33.8), respectively (HR, 1.1; 95% CI, 0.9-1.3). In patients without baseline corticosteroids, mOS was 31.3 months (95% CI, 28.6-34.8) with NIVO + RT + TMZ vs 33.0 months (95% CI, 31.0-35.1) with PBO + RT + TMZ (HR, 1.1; 95% CI, 0.9-1.4). Grade 3/4 treatment-related adverse event rates were 52.4% vs 33.6%, respectively. Conclusions: NIVO added to RT + TMZ did not improve survival in patients with newly diagnosed glioblastoma with methylated or indeterminate MGMT promoter. No new safety signals were observed.

Original languageEnglish
Pages (from-to)1935-1949
Number of pages15
JournalNeuro-oncology
Volume24
Issue number11
DOIs
StatePublished - Nov 1 2022

Keywords

  • MGMT promoter
  • PD-L1
  • glioblastoma
  • nivolumab
  • temozolomide

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