TY - JOUR
T1 - Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, IDH-wildtype
T2 - Post Hoc Analysis of the EORTC Randomized Phase III CATNON Trial
AU - Tesileanu, C. Mircea S.
AU - Sanson, Marc
AU - Wick, Wolfgang
AU - Brandes, Alba A.
AU - Clement, Paul M.
AU - Erridge, Sara C.
AU - Vogelbaum, Michael A.
AU - Nowak, Anna K.
AU - Baurain, Jean Francois
AU - Mason, Warren P.
AU - Wheeler, Helen
AU - Chinot, Olivier L.
AU - Gill, Sanjeev
AU - Griffin, Matthew
AU - Rogers, Leland
AU - Taal, Walter
AU - Rudà, Roberta
AU - Weller, Michael
AU - McBain, Catherine
AU - Van Linde, Myra E.
AU - Aldape, Kenneth
AU - Jenkins, Robert B.
AU - Kros, Johan M.
AU - Wesseling, Pieter
AU - Von Deimling, Andreas
AU - Hoogstrate, Youri
AU - De Heer, Iris
AU - Atmodimedjo, Peggy N.
AU - Dubbink, Hendrikus J.
AU - Brouwer, Rutger W.W.
AU - Van IJcken, Wilfred F.J.
AU - Cheung, Kin Jip
AU - Golfinopoulos, Vassilis
AU - Baumert, Brigitta G.
AU - Gorlia, Thierry
AU - French, Pim J.
AU - Van Den Bent, Martin J.
N1 - Publisher Copyright:
©2022 American Association for Cancer Research.
PY - 2022/6/15
Y1 - 2022/6/15
N2 - 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.
AB - 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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U2 - 10.1158/1078-0432.CCR-21-4283
DO - 10.1158/1078-0432.CCR-21-4283
M3 - Article
C2 - 35275197
AN - SCOPUS:85131902927
SN - 1078-0432
VL - 28
SP - 2527
EP - 2535
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 12
ER -