Prognostic Markers of DNA Methylation and Next-Generation Sequencing in Progressive Glioblastoma from the EORTC-26101 Trial

Tobias Kessler*, Daniel Schrimpf, Laura Doerner, Ling Hai, Leon D. Kaulen, Jakob Ito, Martin van den Bent, Martin Taphoorn, Alba A. Brandes, Ahmed Idbaih, Julien Dômont, Paul M. Clement, Mario Campone, Martin Bendszus, Andreas von Deimling, Felix Sahm, Michael Platten, Wolfgang Wick, Antje Wick

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)
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Abstract

PURPOSE: 

The EORTC-26101 study was a randomized phase II and III clinical trial of bevacizumab in combination with lomustine versus lomustine alone in progressive glioblastoma. Other than for progression-free survival (PFS), there was no benefit from addition of bevacizumab for overall survival (OS). However, molecular data allow for the rare opportunity to assess prognostic biomarkers from primary surgery for their impact in progressive glioblastoma. 

EXPERIMENTAL DESIGN: 

We analyzed DNA methylation array data and panel sequencing from 170 genes of 380 tumor samples of the EORTC-26101 study. These patients were comparable with the overall study cohort in regard to baseline characteristics, study treatment, and survival.

RESULTS: 

Of patients' samples, 295/380 (78%) were classified into one of the main glioblastoma groups, receptor tyrosine kinase (RTK)1, RTK2 and mesenchymal. There were 10 patients (2.6%) with isocitrate dehydrogenase mutant tumors in the biomarker cohort. Patients with RTK1 and RTK2 classified tumors had lower median OS compared with mesenchymal (7.6 vs. 9.2 vs. 10.5 months). O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation was prognostic for PFS and OS. Neurofibromin (NF)1 mutations were predictive of response to bevacizumab treatment.

CONCLUSIONS: 

Thorough molecular classification is important for brain tumor clinical trial inclusion and evaluation. MGMT promoter methylation and RTK1 classifier assignment were prognostic in progressive glioblastoma. NF1 mutation may be a predictive biomarker for bevacizumab treatment.

Original languageEnglish
Pages (from-to)3892-3900
Number of pages9
JournalClinical Cancer Research : an official journal of the American Association for Cancer Research
Volume29
Issue number19
DOIs
Publication statusPublished - 1 Oct 2023

Bibliographical note

Publisher Copyright:
©2023 The Authors; Published by the American Association for Cancer Research.

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