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). OS and QoL are particularly important parameters since previous randomized trials investigating BEV in primary therapy of GBM have not been able to demonstrate an OS benefit and have yielded conflicting results regarding 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 domaines of the EORTC-QLQ C30 and BN20 questionnaires (global health status, physical functioning, social functioning, motor dysfunction, communication deficit as prespecified domaines), 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 8.7-10.5 months, p=0.0004; hazard ratio 0.56, 95%CI 0.4-0.79). At progression, the crossover rate was similar in both arms (60.8 and 61.9%). Final OS results will be presented. In all prespecified dimensions of QoL, the time to deterioration was not significantly different between the treatment arms. Data of post-progression QoL will be presented. Conclusions: BEV/IRI therapy was superior to TMZ regarding PFS. BEV/IRI therapy did not alter QoL as compared to TMZ therapy. Clinical trial information: No.: 2009-010390-21.