Bevacizumab for Glioblastoma Treatment: Reviewing Biological and Clinical Hypothesis for its Success and Failures

Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor in adults with a very poor prognosis. The standard treatment for newly diagnosed glioblastoma is surgical debulking followed by radiotherapy and temozolomide (TMZ) with additional maintenance with TMZ. However, this regimen offers modest benefits with a median survival of less than 15 months, with an inevitable recurrence.

GBM is one of the most vascularized tumors; therefore antiangiogenic therapeutic strategies are very appealing. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, was the first FDA approved angiogenesis inhibitor, based on impressive response rates in recurrent GBM. Recent trials have shown that the combination of bevacizumab with standard radiotherapy–TMZ for the treatment of newly diagnosed glioblastoma resulted in improved median progressionfree survival, without gain in overall survival. Data regarding quality of life and functional status are conflicting. Not surprisingly, there was an increase in adverse events associated with bevacizumab therapy, namely thrombosis, bleeding and hypertension. Therefore, the efficacy of antiangiogenic therapy in the management of GBM remains unclear. To improve outcomes, it has been made a huge effort to better understand the biology underlying angiogenesis and tumor survival, as well as the mechanisms of antiangiogenic resistance in GBM.

Keywords: Angiogenesis, Antiangiogenic, Bevacizumab, Biomarkers, Central nervous system, Glioblastoma, Glioma, Quality of life, Resistance, Response, Safety, Survival, VEGF.