Citations 1
Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, IDH -wildtype: Post Hoc Analysis of the EORTC Randomized Phase III CATNON T
Tesileanu, C. Mircea S. , Wick, Wolfgang , Clément, Paul M. , Erridge, Sara , Vogelbaum, Michael A. , Nowak, Anna K. , Baurain, Jean‐François , Mason, Warren , Wheeler, Helen , Gill, Sanjeev , Griffin, Matthew, Rogers, Leland , Taal, Walter , Weller, Michael , McBain, Catherine , Linde, Myra E. van , Aldape, Kenneth , Jenkins, Robert B., Hoogstrate, Youri , Heer, Iris de , Atmodimedjo, Peggy N., Dubbink, Hendrikus J. , IJcken, Wilfred F. J. van , Cheung, Kin Jip, Golfinopoulos, Vassilis, Baumert, Brigitta G. , Gorlia, Thierry, French, Pim J. , Bent, Martin J. van den , Sanson, Marc , Wick, Wolfgang , Clement, Paul M , Nowak, Anna K , Baurain, Jean-Francois , Wheeler, Helen , Chinot, Olivier L , Taal, Walter , Weller, Michael , Aldape, Kenneth , Kros, Johan M. , Wesseling, Pieter , von Deimling, Andreas , Hoogstrate, Youri , Dubbink, Hendrikus J , van IJcken, Wilfred F J , Golfinopoulos, Vassilis , French, Pim J , van den Bent, Martin J , Sanson, Marc , Brandes, Alba Ariela , Chinot, Olivier , Rudà, Roberta , Wesseling, Pieter , Deimling, Andreas von , Brouwer, Rutger W. W.
Clinical Cancer Research | March 11, 2022 | Volume: 28 | Issue: 12 | Pages: 2527-2535
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.