LBA15 - Randomized Multicenter Phase II Trial of Irinotecan and Bevacizumab as Neo-Adjuvant and Adjuvant to Temozolomide-Based Chemoradiation Versus Chemoradiation for Unresectable Glioblastoma (DEFINITIVE RESULTS OF THE TEMAVIR ANOCEF STUDY)

Abstract

ABSTRACT Background The prognosis of unresectable glioblastoma (GBM) remains poor despite temozolomide (TMZ)- based chemoradiation. Activity of bevacizumab/irinotecan has been reported in recurrent GBM (Vredenburgh, 2007). We evaluate irinotecan (IRI) and bevacizumab (BVZ) as neo-adjuvant and adjuvant to TMZ-based chemoradiation for unresectable glioblastoma. Method Pts with de novo unresectable GBM, aged 18-70, and KPS > 50, and RPA class 5 were eligible. Experimental arm (A) consisted of neo-adjuvant BVZ 10 mg/kg and IRI 125 mg/m2, every 2 wk for 4 cycles before radiotherapy (60 Gy in 30 fractions) with concurrent TMZ 75 mg/m2/day and BVZ every 2 wk. Adjuvant BVZ and IRI were given every 2 wk for 6 months. The control arm (B) consisted of concomitant TMZ, 75 mg/m2/d during radiotherapy and 150-200 mg/m2 for 5 d every 28 d for 6 months. Cross over were allowed at progression. The inclusion of 60 pts/arm was planned using Fleming's 2 steps design aiming at an increase of PFS at 6 month (PFS6) from 50 % to 66 %, with unilateral alpha 5% and 80% power. Final analysis, including overall survival (OS), was performed 16 months after the end of inclusion. Results Patients (120) were included from April 2009 to January 2011. Clinical factors were well balanced between arms. Treatment-related serious adverse events were brain haemorrhages (3; 3 fatal), biliary or digestive perforation/infection (3, 1 fatal), thrombo-embolism (4, 0 fatal) in Arm A, and biliary or digestive perforation/infection (2, 0 fatal), pulmonary infection (1, no fatal), thrombo-embolism (2, 0 fatal), thrombo- and/or neutrepenia (4, 0 fatal) in arm B. PFS at 6 and 12 months appears to be longer in arm A, but OS was similar in both arms (table). ARM (patients) PFS 6 % [IC95, %] PFS 12 % [IC95, %] OS 6 % [IC95, %] OS 12 % [IC95, %] A (60) 65 [51-75] 31 [20-43] 75 [62-84] 48 [34-60] B (60) 41 [29 -53] 18 [9-28] 72 [59-82] 50 [36-62] Conclusion Despite a trend to a better PFS at 6 and 12 month in the experimental arm, overall survival was not different between arms. Disclosure B. Chauffert: Bruno Chauffert was granted by Roche for travels and attending on several meetings about neuro-oncology. He did not receive any salary or indemnity for coodinating this trial. O. Chinot: Pr Olivier Chinot is the international coordonator of the AVAGLIO trial that is sponsored by Roche. All other authors have declared no conflicts of interest.