Quality of life in the GLARIUS trial randomizing bevacizumab/irinotecan versus temozolomide in newly diagnosed, MGMT-nonmethylated glioblastoma

Abstract

Background: The GLARIUS trial, which investigated the efficacy of bevacizumab (BEV)/irinotecan (IRI) compared with standard temozolomide in the first-line therapy of O6-methylguanine-DNA methyltransferase (MGMT)-nonmethylated glioblastoma, showed that progression-free survival was significantly prolonged by BEV/IRI, while overall survival was similar in both arms. The present report focuses on quality of life (QoL) and Karnofsky performance score (KPS) during the whole course of the disease.

Methods: Patients (n = 170) received standard radiotherapy and were randomized (2:1) for BEV/IRI or standard temozolomide. At least every 3 months KPS was determined and QoL was measured using the European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life and 20-item Brain Neoplasm questionnaires. A generalized estimating equation (GEE) model evaluated differences in the course of QoL and KPS over time. Also, the time to first deterioration and the time to postprogression deterioration were analyzed separately.

Results: In all dimensions of QoL and KPS, GEE analyses and time to first deterioration analyses did not detect significant differences between the treatment arms. At progression, 82% of patients receiving second-line therapy in the standard arm received BEV second-line therapy. For the dimensions of motor dysfunction and headaches, time to postprogression deterioration was prolonged in the standard arm receiving crossover second-line BEV in the vast majority of patients at the time of evaluation.

Conclusions: GLARIUS did not find indications for a BEV-induced detrimental effect on QoL in first-line therapy of MGMT-nonmethylated GBM patients. Moreover, GLARIUS provided some indirect corroborative data supporting the notion that BEV may have beneficial effects upon QoL in relapsed GBM.

Trial registration: ClinicalTrials.gov NCT00967330.

Fig. 1

Development over time in 6 selected domains of QoL according to the EORTC QLQ C30 and BN20 questionnaires. For functional scales a high number means high functionality, for symptom scales high numbers mean a high symptom burden. Median PFS was 5.99 months in the standard arm and 9.7 months in the experimental arm.

Fig. 2

Development over time in KPS, MMSE, and 2 selected domains of QoL according to the EORTC QLQ C30 and BN20 questionnaires. For functional scales a high number means high functionality, for symptom scales high numbers mean a high symptom burden. Median PFS was 5.99 months in the standard arm and 9.7 months in the experimental arm. (A) QoL, KPS, and MMSE prior to tumor progression. (B) Postprogression QoL, KPS, and MMSE.

Fig. 3

Kaplan–Meier plot of time to first deterioration irrespective of disease progression. Deterioration was assumed if symptom scores increased by 10 points or more or functional scores decreased by 10 points or more. Median PFS was 5.99 months in the standard arm and 9.7 months in the experimental arm. (A) Six selected domains of QoL. (B) Irinotecan-induced gastrointestinal toxicity affecting QoL.

Fig. 4

Time to postprogression deterioration of QoL in 6 selected domains. Deterioration was assumed if symptom scores increased by 10 points or more or functional scores decreased by 10 points or more.