Temozolomide and radiotherapy versus radiotherapy alone in patients with glioblastoma, IDH-wildtype: post-hoc analysis of the EORTC randomized phase 3 CATNON trial.
Temozolomide and radiotherapy versus radiotherapy alone in patients with glioblastoma, IDH-wildtype: post-hoc analysis of the EORTC randomized phase 3 CATNON trial.
复制标题
替莫唑胺联合放疗与单独放疗治疗 IDH 野生型胶质母细胞瘤患者：EORTC 随机 3 期 CATNON 试验的事后分析。
DOI：
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复制
发表时间：
2022
影响因子：
11.5
通讯作者：
M. J. van den Bent
中科院分区：
文献类型：
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作者：
C. M. S. Tesileanu;M. Sanson;W. Wick;A. Brandes;P. Clement;S. Erridge;M. Vogelbaum;A. Nowak;J. Baurain;W. Mason;H. Wheeler;O. Chinot;S. Gill;M. Griffin;L. Rogers;W. Taal;R. Rudà;M. Weller;C. Mcbain;M. V. van Linde;K. Aldape;R. Jenkins;J. Kros;P. Wesseling;A. von Deimling;Y. Hoogstrate;I. D. de Heer;P. Atmodimedjo;H. Dubbink;R. Brouwer;W. V. van Ijcken;Kin‐Jip Cheung;V. Golfinopoulos;B. Baumert;T. Gorlia;P. French;M. J. van den Bent
目的
PURPOSE
In a post-hoc analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with IDH1/2wt anaplastic astrocytomas with molecular features of glioblastoma (redesignated as glioblastoma, IDH-wildtype in the 2021 WHO classification of CNS tumors).
EXPERIMENTAL DESIGN
From the randomized phase 3 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. 159 of these tumors met the WHO 2021 molecular criteria for glioblastoma, IDH-wildtype. 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%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-wildtype 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.