Randomized phase II trial of irinotecan and bevacizumab as neo-adjuvant and adjuvant to temozolomide-based chemoradiation compared to temozolomide-chemoradiation for unresectable glioblastoma. Final results of the TEMAVIR study from ANOCEF
Mené sur 120 patients atteints d'un glioblastome non résécable (âge : 18 à 70 ans), cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement néo-adjuvant ou adjuvant par bévacizumab et irinotécan en combinaison avec une chimioradiothérapie à base de témozolomide
Background : Prognosis of unresectable glioblastoma remains poor despite temozolomide-based chemoradiation. Activity of bevacizumab (BEV) and irinotecan (IRI) has been reported in recurrent disease. We evaluated BEV and IRI as neo-adjuvant and adjuvant treatment combined with temozolomide-based chemoradiation for unresectable glioblastoma. Patients and Methods : Patients with unresectable glioblastoma, age 18-70, IK>50 were eligible. The experimental arm (BEV/IRI) consisted of neo-adjuvant intravenous BEV, 10 mg/kg, and IRI, 125 mg/m2, every 2 weeks for 4 cycles before radiotherapy (60 Gy), concomitant oral temozolomide, 75 mg/m2/day, and BEV, 10 mg/kg every 2 weeks. Adjuvant BEV and IRI were given every 2 weeks for 6 months. The control arm consisted of concomitant oral temozolomide, 75 mg/m2/day during radiotherapy, and 150-200 mg/m2 for 5 days every 28 days for 6 months. Use of bevacizumab was allowed at progression in the control arm. Results : Patients (120) were included from April 2009 to January 2011. The working hypothesis was that treatment would increase the progression free survival at 6 month (PFS-6 ) from 50 to 66 %. The primary objective was not achieved, and only 30/60 patients were alive without progression at 6 months (50.0% (IC95% [36.8; 63.1]) in the BEV/IRI arm when 37/60 patients were required according to the Fleming decision rules. PFS-6 was 7.1 months in BEV/IRI versus 5.2 months in the control arm. Median overall survival was not different between the two arms (11.1 months). Main toxicities were 3 fatal intracranial bleedings, 3 bile duct or digestive perforations/infections (1 fatal), and 6 thrombotic episodes in BEV/IRI arm, whereas there was 1 intracranial bleeding, 2 bile duct or digestive perforations/infections (1 fatal) and 1 thrombotic episode in the control arm. Conclusion : Neo-adjuvant and adjuvant BEV/IRI, combined with temozolomide-radiation, is not recommended for further evaluation in first line treatment of unresectable glioblastoma. Clinical trial registered under EUDRACT number 2008-002775-28 (NCT01022918).
Annals of Oncology 2014