Bevacizumab for glioblastoma: current indications, surgical implications, and future directions

Abstract

Initial enthusiasm after promising Phase II trials for treating recurrent glioblastomas with the antiangiogenic drug bevacizumab—a neutralizing antibody targeting vascular endothelial growth factor—was tempered by recent Phase III trials showing no efficacy for treating newly diagnosed glioblastomas. As a result, there is uncertainty about the appropriate indications for the use of bevacizumab in glioblastoma treatment. There are also concerns about the effects of bevacizumab on wound healing that neurosurgeons must be aware of. In addition, biochemical evidence suggests a percentage of tumors treated with bevacizumab for an extended period of time will undergo transformation into a more biologically aggressive and invasive phenotype with a particularly poor prognosis. Despite these concerns, there remain numerous examples of radiological and clinical improvement after bevacizumab treatment, particularly in patients with recurrent glioblastoma with limited therapeutic options. In this paper, the authors review clinical results with bevacizumab for glioblastoma treatment to date, ongoing trials designed to address unanswered questions, current clinical indications based on existing data, neurosurgical implications of bevacizumab use in patients with glioblastoma, the current scientific understanding of the tumor response to short- and long-term bevacizumab treatment, and future studies that will need to be undertaken to enable this treatment to fulfill its therapeutic promise for glioblastoma.

Effect of valproic acid on overall survival in patients with high-grade gliomas undergoing temozolomide

“…Previous study demonstrated that although the addition of bevacizumab to standard treatment regimens did not improve OS in newly diagnosed glioblastoma, but was associated with higher rate of response and 6-month progression-free survival in recurrent glioblastoma. [ 45 ] Fountzilas et al reported that bevacizumab in combination with VPA induced a prolonged partial response in a patient with recurrent glioblastoma. [ 46 ] Our study showed VPA has no survival benefit in patient with bevacizumab, however the dose and duration of bevacizumab were not recorded, thus further detailed studies are warranted.…”

Imaging-guided precision medicine in glioblastoma patients treated with immune checkpoint modulators: research trend and future directions in the field of imaging biomarkers and artificial intelligence

“…The oral alkylating agent Temozolomide (TMZ) is used as concomitant and adjuvant chemotherapy at a dose of 75 mg/m 2 daily, throughout the radiation therapy [8]. In cases of disease recurrence after this protocol, the treatment may involve a new surgery, new radiation therapy or the use of bevacizumab (antibody targeting VEGF) [9].…”

An autopsy case of widespread brain dissemination of glioblastoma unnoticed by magnetic resonance imaging after treatment with bevacizumab

“…It has obtained accelerated approval by the United States Food and Drug Administration in May 2009. [4] However, further clinical studies showed no improvement of overall survival (OS) in patients treated with bevacizumab compared to those receiving placebo, although progression-free survival (PFS) was prolonged in the bevacizumab group. [2,5,6,9]…”