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

authors

• Tesileanu C. Mircea S.
• Sanson Marc
• Wick Wolfgang
• Brandes Alba
• Clement Paul
• Erridge Sara
• Vogelbaum Michael
• Nowak Anna
• Baurain Jean-Francois
• Mason Warren
• Wheeler Helen
• Chinot Olivier
• Gill Sanjeev
• Griffin Matthew
• Rogers Leland
• Taal Walter
• Rudà Roberta
• Weller Michael
• Mcbain Catherine
• van Linde Myra
• Aldape Kenneth
• Jenkins Robert
• Kros Johan
• Wesseling Pieter
• von Deimling Andreas
• Hoogstrate Youri
• de Heer Iris
• Atmodimedjo Peggy
• Dubbink Hendrikus
• Brouwer Rutger W.W.
• van Ijcken Wilfred F.J.
• Cheung Kin Jip
• Golfinopoulos Vassilis
• Baumert Brigitta
• Gorlia Thierry
• French Pim
• van den Bent Martin

document type

abstract

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.

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