Similar overall survival with reduced vs. standard dose bevacizumab monotherapy in progressive glioblastoma

Abstract

Introduction: Bevacizumab has demonstrated activity in glioblastoma (GBM), but the true benefits and optimal dose-schedule are debated. A lower dose-schedule than standard-dose bevacizumab (10 mg/kg 2-weekly) might offer similar benefits with lower costs. At our Institution, patients are randomly assigned at time of primary diagnosis to Neuro-Oncologists, who have varying practices in terms of bevacizumab dose-schedule upon progression. Methods: In a retrospective analysis we examined overall survival (OS), measured from first administered bevacizumab dose until death, according to dose-schedule.Patients with de novo WHO Grade IV GBM who received standard-or reduced-dose (5 mg/kg 2-weekly) bevacizumab were included. MGMT methylation status and time from diagnosis to bevacizumab start were examined as prognostic variables.Clinical benefit and a comparative cost analysis were assessed. Results: In total, 1127 bevacizumab doses were administered to 118 patients [Median: 7, Range: 1-44]. Median OS (mOS) was 5.8 months. 69 (59%) patients received standard-dose bevacizumab (mOS: 5.97 months) and 49 patients received reduced-dose (mOS: 5.7 months). No statistically significant difference in OS between dosing schedule was seen (HR: 1.11, P-value: .584). Patients with MGMT methylated tumors (43%) had improved OS compared to those with unmethylated tumors; 7.03 vs 4.97 months (HR: 0.61, P-value: .027). If all patients were treated with reduced-dose bevacizumab, an estimated €2.4M cost reduction would be observed. Conclusions: In this retrospective study, reduced-dose bevacizumab schedule resulted in similar OS to standard-dose bevacizumab monotherapy with substantial cost savings. MGMT methylation appears to convey a survival benefit in the setting of bevacizumab treatment for progressive GBM. K E Y W O R D Sbevacizumab, cost analysis, glioblastoma, MGMT, overall survival, reduced dose 470 | GLEESON Et aL.

Molecular Biomarkers in Glioblastoma: A Systematic Review and Meta-Analysis

“…Wick et al reported MGMT methylation as positive prognostic biomarker in the recurrent GBM patients treated with either bevacizumab or combination of bevacizumab and lomustine (HR: 0.48; p < 0.001) [ 60 ]. Similar findings were reported by Gleeson et al with better OS observed in patients with MGMT methylated tumours as compared to those with unmethylated tumours (HR:0.61, p = 0.027) [ 61 ].…”

“…In these 4 studies, patients were treated with either bevacizumab alone or in combination with other drugs [ 15 , 28 , 30 , 39 ]. The prognostic significance of MGMT methylation for progressive GBM patients treated with bevacizumab has been reported previously [ 60 , 61 ]. Wick et al reported MGMT methylation as positive prognostic biomarker in the recurrent GBM patients treated with either bevacizumab or combination of bevacizumab and lomustine (HR: 0.48; p < 0.001) [ 60 ].…”

Bevacizumab and Atezolizumab for Unresectable Hepatocellular Carcinoma: Real-world Data in Taiwan-Tainan Medical Oncology Group H01 Trial

“…No new safety information was reported but a lower rate of grade 3 or above hypertension was observed (16). In a retrospective analysis of 118 patients with progressive glioblastoma, the OS of patients treated with reduced dose (5 mg/kg 2-weekly) of bevacizumab was not inferior to that in those treated with standard dose (10 mg/kg 2-weekly) of bevacizumab monotherapy in Ireland (17).…”

Natural killer cell therapy potentially enhances the antitumor effects of bevacizumab plus irinotecan in a glioblastoma mouse model

“…Bev (Avastin ® ) and Iri-HCl (Campto ® ) were purchased from Roche (Basel, Switzerland) and Inno.N (Seoul, Republic of Korea) laboratories, respectively. Dose treatments were set at 10 mg/kg Bev plus 125 mg/m 2 Iri-HCl (a high dose of Bev and Iri, Bev plus Iri high ) and 5 mg/kg Bev plus 60 mg/m 2 Iri (a low dose of Bev and Iri, Bev plus Iri low ) according to the previously reported clinical trial dose ( 29 – 32 ). The dose was converted from a human dose into a mouse dose for treatment ( 33 ).…”