QL-13 * QUALITY OF LIFE AND COGNITIVE FUNCTIONING IN THE RANDOMIZED, MULTICENTER GLARIUS TRIAL INVESTIGATING BEVACIZUMAB/IRINOTECAN VS STANDARD TEMOZOLOMIDE IN NEWLY DIAGNOSED, MGMT-NON-METHYLATED GLIOBLASTOMA PATIENTS

Abstract

BACKGROUND: In the GLARIUS trial, progression-free survival was significantly prolonged and overall survival was similar in both arms. The present report focuses on quality of life (QoL), Karnofsky performance score (KPS) and cognitive functioning during first-line and postprogression therapy. METHODS: Patients (n = 170) with newly diagnosed, MGMT-non-methylated glioblastoma were randomized 2:1 for bevacizumab (BEV)/irinotecan (IRI) therapy or standard temozolomide (TMZ) therapy. Every 3 months, KPS, QoL (EORTC-QLQ C30 and BN20) and cognitive functioning (MMSE) was determined. Analysis included a longitudinal mixed model analysis and a Kaplan-Meier analysis of the time to deterioration (10 points in QoL, points, 3 points in MMSE, 20% in KPS; tumor progression not regarded as an event). RESULTS: In KPS, MMSE and all 5 prespecified dimensions of QoL (global health status, physical functioning, social functioning, motor dysfunction, communication deficit) mixed model analyses and time to first deterioration analyses did not detect differences between the treatment arms. Time to deterioration of nausea/vomiting was shorter with BEV/IRI (p = 0.024). At progression, the crossover rate in the BEV/IRI arm (to TMZ) and in the standard TMZ arm (to BEV/(IRI) was identical with 65%. Time to postprogression deterioration was significantly longer in the standard TMZ arm receiving crossover BEV/(IRI) in the majority of patients regarding 13 of 26 QoL dimensions including prespecified global health status, social functioning, motor dysfunction, communication deficit. Time to postprogression deterioration was similar for MMSE, but for KPS it tended to be prolonged in the standard arm receiving crossover BEV/(IRI) (p = 0.09). CONCLUSION: Except for IRI-induced nausea/vomiting, first-line BEV/IRI therapy was not associated with any detrimental effects on QoL, performance status or cognition as compared to TMZ standard therapy. After progression, patients pretreated with TMZ in the standard arm had a prolonged stabilization of QoL in many dimensions presumably due to a high rate of crossover BEV therapy.