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The Capital Region of Denmark - a part of Copenhagen University Hospital
E-pub ahead of print

Radiotherapy Combined With Nivolumab or Temozolomide for Newly Diagnosed Glioblastoma With Unmethylated MGMT Promoter: An International Randomized Phase 3 Trial

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

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  • Antonio Omuro
  • Alba A Brandes
  • Antoine F Carpentier
  • Ahmed Idbaih
  • David A Reardon
  • Timothy Cloughesy
  • Ashley Sumrall
  • Joachim Baehring
  • Martin van den Bent
  • Oliver Bähr
  • Giuseppe Lombardi
  • Paul Mulholland
  • Ghazaleh Tabatabai
  • Ulrik Lassen
  • Juan Manuel Sepulveda
  • Mustafa Khasraw
  • Elodie Vauleon
  • Yoshihiro Muragaki
  • Anna Maria Di Giacomo
  • Nicholas Butowski
  • Patrick Roth
  • Xiaozhong Qian
  • Alex Z Fu
  • Yanfang Liu
  • Von Potter
  • Alexandros-Georgios Chalamandaris
  • Kay Tatsuoka
  • Michael Lim
  • Michael Weller
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BACKGROUND: Addition of temozolomide (TMZ) to radiotherapy (RT) improves overall survival (OS) in glioblastoma, but previous studies suggest that patients with tumors harboring an unmethylated MGMT promoter derive minimal benefit. The aim of this open-label, phase 3 CheckMate 498 study was to evaluate the efficacy of nivolumab (NIVO)+RT compared with TMZ+RT in newly diagnosed glioblastoma with unmethylated MGMT promoter.

METHODS: Patients were randomized 1:1 to standard RT (60 Gy) + NIVO (240 mg every 2 weeks for 8 cycles, then 480 mg every 4 weeks) or RT+TMZ (75 mg/m 2 daily during RT and 150-200 mg/m 2/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 was 13.4 months (95% CI, 12.6-14.3) with NIVO+RT and 14.9 months (95% CI, 13.3-16.1) with TMZ+RT (hazard ratio [HR], 1.31; 95% CI, 1.09-1.58; P=0.0037). Median progression-free survival was 6.0 months (95% CI, 5.7-6.2) with NIVO+RT and 6.2 months (95% CI, 5.9-6.7) with TMZ+RT (HR, 1.38; 95% CI, 1.15-1.65). 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 median OS 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 standard of care for glioblastoma.

Original languageEnglish
JournalNeuro-Oncology
ISSN1522-8517
DOIs
Publication statusE-pub ahead of print - 14 Apr 2022

Bibliographical note

© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

ID: 79475848