O10.04 * THE RANDOMIZED, MULTICENTER GLARIUS TRIAL INVESTIGATING BEVACIZUMAB/IRINOTECAN VS STANDARD TEMOZOLOMIDE IN NEWLY DIAGNOSED, MGMT-NON-METHYLATED GLIOBLASTOMA PATIENTS: FINAL SURVIVAL RESULTS AND QUALITY OF LIFE

BACKGROUND: There is a need for more effective therapies in newly diagnosed glioblastoma (GBM) patients with an MGMT-non-methylated tumor. The GLARIUS trial explored the efficacy of bevacizumab (BEV) + Irinotecan (IRI) as compared to standard TMZ in the first-line therapy of MGMT-non-methylated GBM. The primary endpoint progression-free survival after 6 months (PFS-6) has already been reported as being markedly increased in the BEV/IRI arm (Herrlinger et al., ASCO 2013, LBA 2000). The present report focuses on progression-free survival, overall survival (OS) and quality of life (QoL). METHODS: Patients (n = 170) with newly diagnosed, MGMT-non-methylated glioblastoma received local radiotherapy (RT, 30 x 2 Gy) and were randomized (2:1) for experimental therapy with BEV (10 mg/kg q2w) during RT followed by maintenance BEV (10 mg/kg q2w) + IRI (125 mg/m2 q2w) or standard therapy with daily TMZ (75 mg/m2) during RT followed by 6 courses of TMZ (150-200 mg/m2/day for 5 days q4w). For 5 prespecified dimensions of the EORTC-QLQ C30 and BN20 questionnaires (global health status, physical functioning, social functioning, motor dysfunction, communication deficit as prespecified domains), the time to deterioration by at least 10 points was analyzed using Kaplan-Meier statistics. RESULTS: With BEV/IRI, PFS was significantly prolonged from a median of 5.9 months (95%CI 2.7-6.2 months) to 9.7 months (95%CI 8.5-10.6 months, p < 0.0001; hazard ratio 0.57, 95%CI 0.41-0.79). At progression, the crossover rate was 60.4% (TMZ to BEV/(IRI) and 61.9% (BEV/IRI to TMZ). OS did not show any difference between the two arms: median OS was 16.6 months (95%CI 15.4-18.35 months) in the BEV/IRI arm and 17.3 months (95%CI 14.8-20.4 months). In all prespecified dimensions of QoL, the time to deterioration was not significantly different between the treatment arms. CONCLUSION: BEV/IRI therapy was superior to TMZ regarding PFS but OS was not prolonged. BEV/IRI therapy did not alter QoL as compared to TMZ therapy.