Titre :

Zotiraciclib (TG02) for newly diagnosed glioblastoma in the elderly or for recurrent glioblastoma: The EORTC 1608 STEAM trial.

Auteur(s) :

Le Rhun, Emilie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Gorlia, T. [Auteur]
Felsberg, J. [Auteur]
Jongen, J. [Auteur]
Maurage, Claude-Alain [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Ducray, F. [Auteur]
Gramatzki, D. [Auteur]
Hau, P. [Auteur]
Chinot, O. L. [Auteur]
Preusser, M. [Auteur]
Cartalat, S. [Auteur]
Roth, P. [Auteur]
Van Den Bent, M. [Auteur]
Furtner, J. [Auteur]
Collienne, M. [Auteur]
Reifenberger, G. [Auteur]
Weller, M. [Auteur]
Universität Zürich [Zürich] = University of Zurich [UZH]

Titre de la revue :

European Journal of Cancer

Nom court de la revue :

Eur J Cancer

Numéro :

198

Pagination :

113475

Éditeur :

Elsevier

Date de publication :

2024-02-03

ISSN :

1879-0852

Mot(s)-clé(s) en anglais :

Astrocytoma
CDK
C-MYC
Chemotherapy
Survival proteins

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Background Zotiraciclib (TG02) is an oral multi-cyclin dependent kinase (CDK) inhibitor thought to inhibit tumor growth via CDK-9-dependent depletion of survival proteins such as c-MYC and MCL-1 which are frequently ...
Lire la suite >Background Zotiraciclib (TG02) is an oral multi-cyclin dependent kinase (CDK) inhibitor thought to inhibit tumor growth via CDK-9-dependent depletion of survival proteins such as c-MYC and MCL-1 which are frequently overexpressed in glioblastoma. Methods EORTC 1608 (NCT03224104) (STEAM) had a three parallel group (A,B,C) phase Ib, open-label, non-randomized, multicenter design in IDH wild-type newly diagnosed glioblastoma or anaplastic astrocytoma. Groups A and B explored the maximum tolerated dose (MTD) of TG02 in elderly patients, in combination with hypofractionated radiotherapy alone (group A) or temozolomide alone (group B), according to O6-methylguanine DNA methyltransferase promoter methylation status determined centrally. Group C explored single agent activity of TG02 at first relapse after temozolomide chemoradiotherapy with a primary endpoint of progression-free survival at 6 months (PFS-6). Tumor expression of CDK-9, c-MYC and MCL-1 was determined by immunohistochemistry. Results The MTD was 150 mg twice weekly in combination with radiotherapy alone (group A) or temozolomide alone (group B). Two dose-limiting toxicities were observed at 150 mg: one in group A (grade 3 seizure), one in group B (multiple grade 1 events). Main toxicities included neutropenia, gastrointestinal disorders and hepatotoxicity. PFS-6 in group C was 6.7%. CDK-9, c-MYC and MCL-1 were confirmed to be expressed and their expression was moderately cross-correlated. High protein levels of MCL-1 were associated with inferior survival. Conclusions TG02 exhibits overlapping toxicity with alkylating agents and low single agent clinical activity in recurrent glioblastoma. The role of CDK-9 and its down-stream effectors as prognostic factors and therapeutic targets in glioblastoma warrants further study.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172
• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Date de dépôt :

2024-06-22T21:33:42Z
2024-12-04T09:06:04Z