Brussels, Belgium, 8 October 2024. A groundbreaking study1 led by Dr Monika E. Hegi, MD, PhD and European Organisation for Research and Treatment of Cancer (EORTC) headquarters team (Felix Oppong Msc, Dr Thierry Gorlia, PhD) reveals that older adults glioblastoma patients with truly unmethylated MGMT promoter do not benefit from temozolomide (TMZ) treatment, challenging current treatment protocols and paving the way for more personalised therapies.
The study reanalysed data from the CE.6 and pooled Nordic/NOA-08 trials, involving 687 patients, to assess the impact of MGMT promoter methylation on TMZ treatment efficacy. Using a specific cutoff established through a pooled analysis of four clinical trials, the research confirmed that patients with truly unmethylated MGMT promoter derived no benefit from TMZ, whether administered alone or in combination with radiotherapy (RT). This finding underscores the necessity of using validated MGMT promoter methylation assays to accurately identify patients who will not benefit from TMZ, thereby reducing unnecessary toxicity and allowing for the exploration of more promising treatment options.
The significance of this study lies in its potential to transform the treatment landscape for older adults glioblastoma patients. By accurately identifying patients who will not benefit from TMZ, healthcare providers can avoid undue toxicity and focus on more effective treatment strategies. The European Organisation for Research and Treatment of Cancer (EORTC) and other collaborating organisations emphasise the importance of stratified patient management to improve outcomes without compromising patient safety.
“This study represents a pivotal moment in the treatment of glioblastoma, particularly for our older adults patients,” says Monika E. Hegi, PhD. “By refining our approach to patient selection, we can significantly enhance treatment efficacy and patient quality of life.”
In conclusion, these findings highlight the critical role of MGMT promoter methylation in guiding treatment decisions for glioblastoma, offering a path toward more personalised and effective therapies.
About EORTC
The European Organisation for Research and Treatment of Cancer (EORTC) is a non-governmental, non-profit organisation, which unites clinical cancer research experts, throughout Europe, to define better treatments for cancer patients to prolong survival and improve quality of life. Spanning from translational to large, prospective, multi-centre, phase III clinical trials that evaluate new therapies and treatment strategies as well as patient quality of life, its activities are coordinated from EORTC Headquarters, a unique international clinical research infrastructure, based in Brussels, Belgium.
Journal
Neuro-Oncology
Method of Research
Data/statistical analysis
Subject of Research
People
Article Title
No benefit from TMZ treatment in glioblastoma with truly unmethylated MGMT promoter: Reanalysis of the CE.6 and the pooled Nordic/NOA-08 trials in elderly glioblastoma patients
Article Publication Date
3-Jul-2024
COI Statement
M.E.H., F.B.O., N.L., R.H., N.J.L., T.G., and A.M. report no conflict of interest.WW reports honoraria for consultation or nonfinancial clinical trial support from Apogenix, Bayer, Merck Sharp & Dome, AstraZeneca, Merck Serono, Novartis, Roche, and Mundipharma, with compensation paid to the Medical Faculty at Heidelberg University. MW has received research grants from Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Bayer, Curevac, Medac, Neurosense, Novartis, Novocure, Orbus, Philogen, Roche, and Servier.