Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, IDH-wildtype: Post Hoc Analysis of the EORTC Randomized Phase III CATNON Trial
Articolo
Data di Pubblicazione:
2022
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 glioblas-toma [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 con-current temozolomide to radiotherapy in anaplastic astrocyto-mas, 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 methyl-ation 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.
Tipologia CRIS:
03A-Articolo su Rivista
Elenco autori:
Tesileanu, C Mircea S; Sanson, Marc; Wick, Wolfgang; Brandes, Alba A; Clement, Paul M; Erridge, Sara C; Vogelbaum, Michael A; Nowak, Anna K; Baurain, Jean-Francois; Mason, Warren P; Wheeler, Helen; Chinot, Olivier L; Gill, Sanjeev; Griffin, Matthew; Rogers, Leland; Taal, Walter; Ruda', Roberta; Weller, Michael; McBain, Catherine; van Linde, Myra E; Aldape, Kenneth; Jenkins, Robert B; Kros, Johan M; Wesseling, Pieter; von Deimling, Andreas; Hoogstrate, Youri; de Heer, Iris; Atmodimedjo, Peggy N; Dubbink, Hendrikus J; Brouwer, Rutger W W; van IJcken, Wilfred F J; Cheung, Kin Jip; Golfinopoulos, Vassilis; Baumert, Brigitta G; Gorlia, Thierry; French, Pim J; van den Bent, Martin J
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