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

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.

• Authors: 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 Linde, Kenneth 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
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 28 Issue 12 Pg. 2527-2535 (06 13 2022) ISSN: 1557-3265 [Electronic] United States
• PMID: 35275197 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2022 American Association for Cancer Research.

Chemical References

• Antineoplastic Agents, Alkylating
• Dacarbazine
• Isocitrate Dehydrogenase
• DNA Modification Methylases
• DNA Repair Enzymes
• Temozolomide

Topics

• Antineoplastic Agents, Alkylating
• Astrocytoma (drug therapy)
• Brain Neoplasms (drug therapy, genetics, radiotherapy)
• DNA Methylation
• DNA Modification Methylases (genetics)
• DNA Repair Enzymes (genetics)
• Dacarbazine
• Glioblastoma (drug therapy, genetics, radiotherapy)
• Humans
• Isocitrate Dehydrogenase (genetics)
• Prospective Studies
• Temozolomide (therapeutic use)