Aflibercept (VEGF Trap): one more double-edged sword of anti-VEGF therapy for cancer?

The use of vascular endothelial growth factor (VEGF)-targeted agents for treating cancer has increased dramatically over recent decades. These drugs provide considerable benefits in terms of progression-free (PFS) or overall (OS) survival for cancer patients. Of particular importance to clinicians treating cancer patients by using VEGF-targeted agents is VEGF-inhibition-induced hypertension, proteinuria, thrombosis and hemorrhage. Aflibercept is a new, successful example of targeting VEGF for therapy of solid tumors. Though results from phase I and II clinical trials demonstrated aflibercept is well tolerated, it inevitably has severe adverse effects unique to this class of agents. In this review, we discuss the adverse effects associated with aflibercept (VEGF Trap), focusing on vascularassociated hypertension, proteinuria, hemorrhage, and thrombosis, and further discuss the mechanisms, significance, and potential management of these adverse effects.