Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, IDH-wildtype: Post Hoc Analysis of the EORTC Randomized Phase III CATNON Trial

C. Mircea S. Tesileanu, Marc Sanson, Wolfgang Wick, Alba A. Brandes, Paul M. Clement, Sara C. Erridge, Michael A. Vogelbaum, Anna K. Nowak, Jean Francois Baurain, Warren P. Mason, Helen Wheeler, Olivier L. Chinot, Sanjeev Gill, Matthew Griffin, Leland Rogers, Walter Taal, Roberta Rudà, Michael Weller, Catherine McBain, Myra E. Van LindeKenneth Aldape, Robert B. Jenkins, Johan M. Kros, Pieter Wesseling, Andreas Von Deimling, Youri Hoogstrate, Iris De Heer, Peggy N. Atmodimedjo, Hendrikus J. Dubbink, Rutger W.W. Brouwer, Wilfred F.J. Van IJcken, Kin Jip Cheung, Vassilis Golfinopoulos, Brigitta G. Baumert, Thierry Gorlia, Pim J. French, Martin J. Van Den Bent

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: In a post hoc analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with IDH1/2 wildtype (wt) anaplastic astrocytomas with molecular features of glioblastoma [redesignated as glioblastoma, isocitrate dehydrogenase- wildtype (IDH-wt) in the 2021 World Health Organization (WHO) classification of central nervous system tumors]. Patients and Methods: From the randomized phase III CATNON study examining the addition of adjuvant and concurrent temozolomide to radiotherapy in anaplastic astrocytomas, we selected a subgroup of IDH1/2wt and H3F3Awt tumors with presence of TERT promoter mutations and/or EGFR amplifications and/or combined gain of chromosome 7 and loss of chromosome 10. Molecular abnormalities including MGMT promoter methylation status were determined by next-generation sequencing, DNA methylation profiling, and SNaPshot analysis. Results: Of the 751 patients entered in the CATNON study, 670 had fully molecularly characterized tumors. A total of 159 of these tumors met the WHO 2021 molecular criteria for glioblastoma, IDH-wt. Of these patients, 47 received radiotherapy only and 112 received a combination of radiotherapy and temozolomide. There was no added effect of temozolomide on either overall survival [HR, 1.19; 95% confidence interval (CI), 0.82-1.71] or progression-free survival (HR, 0.87; 95% CI, 0.61-1.24). MGMT promoter methylation was prognostic for overall survival, but was not predictive for outcome to temozolomide treatment either with respect to overall survival or progression-free survival. Conclusions: In this cohort of patients with glioblastoma, IDH-wt temozolomide treatment did not add benefit beyond that observed from radiotherapy, regardless of MGMT promoter status. These findings require a new well-powered prospective clinical study to explore the efficacy of temozolomide treatment in this patient population.

Original languageEnglish (US)
Pages (from-to)2527-2535
Number of pages9
JournalClinical Cancer Research
Volume28
Issue number12
DOIs
StatePublished - Jun 15 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, IDH-wildtype: Post Hoc Analysis of the EORTC Randomized Phase III CATNON Trial'. Together they form a unique fingerprint.

Cite this