Dose-dependent efficacy of bevacizumab in recurrent glioblastoma

Abstract

BackgroundBevacizumab (BEV), at a standard dose of 10 mg/kg every 2 weeks is associated with prolonged progression-free survival (PFS) but no improvement in overall survival (OS) in recurrent glioblastoma (rGBM). Few studies have examined the potential dose-dependent e cacy of BEV. In Ontario, reimbursement for the costs of BEV varies, and as a result, our practice began to routinely use lower dose regimens. The main aim of this study was to ensure that there was no harm to patients who received the low dose protocol. MethodsA single-center retrospective study of patients given BEV for rGBM between 2015-2020 was performed. Clinical and treatment data including BEV dose regimen (SD [10 mg/kg every 2 weeks] vs LD [5 mg/kg every 2-3 weeks or 10 mg/kg every 3 weeks]) received at the time of rGBM diagnosis were captured.Overall survival (OS) and progression-free survival (PFS) on BEV were compared using the Kaplan-Meier product-limit method. Log-rank test was used to compare potential predictive factors. Cox regression model was performed for multivariable analysis of OS and PFS. ResultsA total of 96 patients were included with a median follow-up duration of 6.84 months (range 1.12-50.63 months) from the date of the rst infusion. The LD group consisted of 55 of the 96 patients. By virtue of funding mechanisms for BEV, the median age in the LD group was signi cantly higher (62 vs 54 years p = 0.009). There was no difference in MGMT status between the 2 groups (p = 0.60). Eight patients received lomustine with BEV (3 from the SD and 5 from the LD. The LD group had prolonged median PFS (5.89 months versus 3.22 months; p = 0.0112) and OS (10.23 months versus 6.28 months; p = 0.0010).Multivariable analysis including the dose of BEV, the extent of resection, gender, and age revealed that standard dose of BEV, subtotal resection, and female sex were associated with worse overall survival.Nine patients in the SD group vs 18 patients in the LD group reported an adverse event related to BEV. ConclusionsFor patients with recurrent GBM, we found that a low dose regimen of BEV was associated with prolonged OS and PFS compared to the standard dose regimen. Lower dose schedules may be a better and more cost-effective option for patients with rGBM. Lower costs might provide more equitable access to this very important palliative drug.

The efficacy and adverse events of bevacizumab combined with temozolomide in the treatment of glioma: a systemic review and meta-analysis of randomized controlled trials

“…Previous studies have shown that antiangiogenic agents have an inhibitory effect on glioblastoma ( 11 ). For the treatment of glioblastoma, BEV can bind to its blood circulation target, change the kinetic relationship between ligand binding to endothelial cells and down-regulate angiogenic signals, so as to achieve the purpose of inhibiting tumor growth ( 12 ). Therefore, BEV is a relatively suitable drug for glioma treatment in combination with TMZ.…”