Bevacizumab Failure in Patients with Recurrent Malignant Glioma

In patients with recurrent malignant glioma, bevacizumab therapy achieves high response rates, prolonged progression-free survival, and reduced corticosteroid requirements. However, progressive disease during bevacizumab therapy is the rule. Resistance to bevacizumab may be mediated by upregulation of alternative pro-angiogenic factors or an infiltrative tumor growth pattern characterized by vascular co-option. Clinically, bevacizumab failure is often followed by rapid progression and death. In patients with progressive disease despite bevacizumab monotherapy, adding cytotoxic chemotherapy has not proven beneficial. Similarly, when patients develop progressive disease despite bevacizumab and chemotherapy, continuing bevacizumab and changing the concurrent chemotherapy agent is not effective. Combining bevacizumab with anti-invasion therapies is an appealing approach that has yet to be investigated in clinical trials. Additional research into mechanisms of resistance to anti-angiogenic therapy is needed in order to develop other promising strategies.