Titre
Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: the randomized, open-label, phase II ARTE trial.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Wirsching, H.G.
Auteure/Auteur
Tabatabai, G.
Auteure/Auteur
Roelcke, U.
Auteure/Auteur
Hottinger, A.F.
Auteure/Auteur
Jörger, F.
Auteure/Auteur
Schmid, A.
Auteure/Auteur
Plasswilm, L.
Auteure/Auteur
Schrimpf, D.
Auteure/Auteur
Mancao, C.
Auteure/Auteur
Capper, D.
Auteure/Auteur
Conen, K.
Auteure/Auteur
Hundsberger, T.
Auteure/Auteur
Caparrotti, F.
Auteure/Auteur
von Moos, R.
Auteure/Auteur
Riklin, C.
Auteure/Auteur
Felsberg, J.
Auteure/Auteur
Roth, P.
Auteure/Auteur
Jones, DTW
Auteure/Auteur
Pfister, S.
Auteure/Auteur
Rushing, E.J.
Auteure/Auteur
Abrey, L.
Auteure/Auteur
Reifenberger, G.
Auteure/Auteur
Held, L.
Auteure/Auteur
von Deimling, A.
Auteure/Auteur
Ochsenbein, A.
Auteure/Auteur
Weller, M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1569-8041
Statut éditorial
Publié
Date de publication
2018-06-01
Volume
29
Numéro
6
Première page
1423
Dernière page/numéro d’article
1430
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Clinical Trial, Phase II ; Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
The addition of bevacizumab to temozolomide-based chemoradiotherapy (TMZ/RT → TMZ) did not prolong overall survival (OS) in patients with newly diagnosed glioblastoma in phase III trials. Elderly and frail patients are underrepresented in clinical trials, but early reports suggested preferential benefit in this population.
ARTE was a 2 : 1 randomized, multi-center, open-label, non-comparative phase II trial of hypofractionated RT (40 Gy in 15 fractions) with bevacizumab (10 mg/kg×14 days) (arm A, N = 50) or without bevacizumab (arm B, N = 25) in patients with newly diagnosed glioblastoma aged ≥65 years. The primary objective was to obtain evidence for prolongation of median OS by the addition of bevacizumab to RT. Response was assessed by RANO criteria. Quality of life (QoL) was monitored by the EORTC QLQ-C30/BN20 modules. Exploratory studies included molecular subtyping by 450k whole methylome and gene expression analyses.
Median PFS was longer in arm A than in arm B (7.6 and 4.8 months, P = 0.003), but OS was similar (12.1 and 12.2 months, P = 0.77). Clinical deterioration was delayed and more patients came off steroids in arm A. Prolonged PFS in arm A was confined to tumors with the receptor tyrosine kinase (RTK) I methylation subtype (HR 0.25, P = 0.014) and proneural gene expression (HR 0.29, P = 0.025). In a Cox model of OS controlling for established prognostic factors, associations with more favorable outcome were identified for age <70 years (HR 0.52, P = 0.018) and Karnofsky performance score 90%-100% (HR 0.51, P = 0.026). Including molecular subtypes into that model identified an association of the RTK II gene methylation subtype with inferior OS (HR 1.73, P = 0.076).
Efficacy outcomes and exploratory analyses of ARTE do not support the hypothesis that the addition of bevacizumab to RT generally prolongs survival in elderly glioblastoma patients. Molecular biomarkers may identify patients with preferential benefit from bevacizumab.
NCT01443676.
ARTE was a 2 : 1 randomized, multi-center, open-label, non-comparative phase II trial of hypofractionated RT (40 Gy in 15 fractions) with bevacizumab (10 mg/kg×14 days) (arm A, N = 50) or without bevacizumab (arm B, N = 25) in patients with newly diagnosed glioblastoma aged ≥65 years. The primary objective was to obtain evidence for prolongation of median OS by the addition of bevacizumab to RT. Response was assessed by RANO criteria. Quality of life (QoL) was monitored by the EORTC QLQ-C30/BN20 modules. Exploratory studies included molecular subtyping by 450k whole methylome and gene expression analyses.
Median PFS was longer in arm A than in arm B (7.6 and 4.8 months, P = 0.003), but OS was similar (12.1 and 12.2 months, P = 0.77). Clinical deterioration was delayed and more patients came off steroids in arm A. Prolonged PFS in arm A was confined to tumors with the receptor tyrosine kinase (RTK) I methylation subtype (HR 0.25, P = 0.014) and proneural gene expression (HR 0.29, P = 0.025). In a Cox model of OS controlling for established prognostic factors, associations with more favorable outcome were identified for age <70 years (HR 0.52, P = 0.018) and Karnofsky performance score 90%-100% (HR 0.51, P = 0.026). Including molecular subtypes into that model identified an association of the RTK II gene methylation subtype with inferior OS (HR 1.73, P = 0.076).
Efficacy outcomes and exploratory analyses of ARTE do not support the hypothesis that the addition of bevacizumab to RT generally prolongs survival in elderly glioblastoma patients. Molecular biomarkers may identify patients with preferential benefit from bevacizumab.
NCT01443676.
PID Serval
serval:BIB_385659ABD730
PMID
Open Access
Oui
Date de création
2018-04-19T17:31:19.869Z
Date de création dans IRIS
2025-05-20T14:58:44Z