Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082).

Détails

Ressource 1Télécharger: BIB_CBAAFBFE2DD4.P001.pdf (8833.42 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_CBAAFBFE2DD4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082).
Périodique
Clinical cancer research
Auteur(s)
Wick W., Gorlia T., Bady P., Platten M., van den Bent M.J., Taphoorn M.J., Steuve J., Brandes A.A., Hamou M.F., Wick A., Kosch M., Weller M., Stupp R., Roth P., Golfinopoulos V., Frenel J.S., Campone M., Ricard D., Marosi C., Villa S., Weyerbrock A., Hopkins K., Homicsko K., Lhermitte B., Pesce G., Hegi M.E.
ISSN
1078-0432 (Print)
ISSN-L
1078-0432
Statut éditorial
Publié
Date de publication
01/10/2016
Peer-reviewed
Oui
Volume
22
Numéro
19
Pages
4797-4806
Langue
anglais
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
Publication Status: ppublish
Résumé
EORTC 26082 assessed the activity of temsirolimus in patients with newly diagnosed glioblastoma harboring an unmethylated O6 methylguanine-DNA-methyltransferase (MGMT) promoter.
Patients (n = 257) fulfilling eligibility criteria underwent central MGMT testing. Patients with MGMT unmethylated glioblastoma (n = 111) were randomized 1:1 between standard chemo-radiotherapy with temozolomide or radiotherapy plus weekly temsirolimus (25 mg). Primary endpoint was overall survival at 12 months (OS12). A positive signal was considered >38 patients alive at 12 months in the per protocol population. A noncomparative reference arm of 54 patients evaluated the assumptions on OS12 in a standard-treated cohort of patients. Prespecified post hoc analyses of markers reflecting target activation were performed.
Both therapies were administered per protocol with a median of 13 cycles of maintenance temsirolimus. Median age was 55 and 58 years in the temsirolimus and standard arms, the WHO performance status 0 or 1 for most patients (95.5%). In the per protocol population, 38 of 54 patients treated with temsirolimus reached OS12. The actuarial 1-year survival was 72.2% [95% confidence interval (CI), 58.2-82.2] in the temozolomide arm and 69.6% (95% CI, 55.8-79.9) in the temsirolimus arm [hazard ratio (HR) 1.16; 95% CI, 0.77-1.76; P = 0.47]. In multivariable prognostic analyses of clinical and molecular factors, phosphorylation of mTORSer2448 in tumor tissue (HR 0.13; 95% CI, 0.04-0.47; P = 0.002), detected in 37.6%, was associated with benefit from temsirolimus.
Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter. Phosphorylation of mTORSer2448 in the pretreatment tumor tissue may define a subgroup benefitting from mTOR inhibition. Clin Cancer Res; 22(19); 4797-806. ©2016 AACR.

Mots-clé
Adult, Aged, Brain Neoplasms/drug therapy, Brain Neoplasms/mortality, Brain Neoplasms/radiotherapy, Chemoradiotherapy/methods, DNA Methylation, DNA Modification Methylases/genetics, DNA Repair Enzymes/genetics, Dacarbazine/administration & dosage, Dacarbazine/analogs & derivatives, Female, Glioblastoma/drug therapy, Glioblastoma/mortality, Glioblastoma/radiotherapy, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Promoter Regions, Genetic/genetics, Proportional Hazards Models, Sirolimus/administration & dosage, Sirolimus/analogs & derivatives, Tumor Suppressor Proteins/genetics, Young Adult
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/05/2016 18:45
Dernière modification de la notice
09/05/2019 1:18
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