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, M. S.Sanson, M.
Wick, W.
Brandes, A. A.
Clement, P. M.
Erridge, S. C.
Vogelbaum, M. A.
Nowak, A. K.
Baurain, J. F.
Mason, W. P.
Wheeler, H.
Chinot, O. L.
Gill, S.
Grif, M.
Rogers, L.
Taal, W.
Ruda, R.
Weller, M.
McBain, Catharine A
van Linde, M. E.
Aldape, K.
Jenkins, R. B.
Kros, J. M.
Wesseling, P.
von Deimling, A.
Hoogstrate, Y.
de Heer, I.
Atmodimedjo, P. N.
Dubbink, H. J.
Brouwer, R. W. W.
Ijcken, W.
Cheung, K. J.
Golfinopoulos, V.
Baumert, B. G.
Gorlia, T.
French, P. J.
van den Bent, M. J.
Affiliation
Neurology Department, Brain Tumor Center, Erasmus MC Cancer Institute, Rotterdam, the NetherlandsIssue Date
2022
Metadata
Show full item recordAbstract
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.Citation
Tesileanu MS, Sanson M, Wick W, Brandes AA, Clement PM, Erridge SC, et al. Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, IDH-wildtype: Post Hoc Analysis of the EORTC Randomized Phase III CATNON Trial. Clinical Cancer Research. 2022 Jun;28(12):2527-35. PubMed PMID: WOS:000814512400001. Pubmed Central PMCID: 9297529.Journal
Clinical Cancer ResearchDOI
10.1158/1078-0432.CCR-21-4283.PubMed ID
35275197Additional Links
https://dx.doi.org/10.1158/1078-0432.CCR-21-4283.Type
Articleae974a485f413a2113503eed53cd6c53
10.1158/1078-0432.CCR-21-4283.
Scopus Count
Collections
Related articles
- A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas.
- Authors: Arita H, Yamasaki K, Matsushita Y, Nakamura T, Shimokawa A, Takami H, Tanaka S, Mukasa A, Shirahata M, Shimizu S, Suzuki K, Saito K, Kobayashi K, Higuchi F, Uzuka T, Otani R, Tamura K, Sumita K, Ohno M, Miyakita Y, Kagawa N, Hashimoto N, Hatae R, Yoshimoto K, Shinojima N, Nakamura H, Kanemura Y, Okita Y, Kinoshita M, Ishibashi K, Shofuda T, Kodama Y, Mori K, Tomogane Y, Fukai J, Fujita K, Terakawa Y, Tsuyuguchi N, Moriuchi S, Nonaka M, Suzuki H, Shibuya M, Maehara T, Saito N, Nagane M, Kawahara N, Ueki K, Yoshimine T, Miyaoka E, Nishikawa R, Komori T, Narita Y, Ichimura K
- Issue date: 2016 Aug 8
- Predictive value of MGMT promoter methylation on the survival of TMZ treated IDH-mutant glioblastoma.
- Authors: Chai R, Li G, Liu Y, Zhang K, Zhao Z, Wu F, Chang Y, Pang B, Li J, Li Y, Jiang T, Wang Y
- Issue date: 2021 Feb 15
- IDH mutation and MGMT promoter methylation are associated with the pseudoprogression and improved prognosis of glioblastoma multiforme patients who have undergone concurrent and adjuvant temozolomide-based chemoradiotherapy.
- Authors: Li H, Li J, Cheng G, Zhang J, Li X
- Issue date: 2016 Dec
- Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial.
- Authors: Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper J, Braun C, Meixensberger J, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M, NOA-08 Study Group of Neuro-oncology Working Group (NOA) of German Cancer Society
- Issue date: 2012 Jul
- Low MGMT digital expression is associated with a better outcome of IDH1 wildtype glioblastomas treated with temozolomide.
- Authors: Gomes I, Moreno DA, Dos Reis MB, da Silva LS, Leal LF, Gonçalves GM, Pereira CA, Oliveira MA, de Medeiros Matsushita M, Reis RM
- Issue date: 2021 Jan