Adverse effects of anticancer agents that target the VEGF pathway

Antiangiogenic agents that target the VEGF pathway have become an important part of standard therapy in multiple cancer indications. Although most adverse effects of VEGF inhibitors are modest and manageable, some are associated with serious and life-threatening consequences. This Review examines the toxicity profiles of anti-VEGF monoclonal antibodies and small-molecule inhibitors and considers the potential mechanisms of the adverse effects, risk factors, and the implications for patient management. Antiangiogenesis agents that target the VEGF/VEGF receptor pathway have become an important part of standard therapy in multiple cancer indications. With expanded clinical experience with this class of agents has come the increasing recognition of the diverse adverse effects related to disturbance of VEGF-dependent physiological functions and homeostasis in the cardiovascular and renal systems, as well as wound healing and tissue repair. Although most adverse effects of VEGF inhibitors are modest and manageable, some are associated with serious and life-threatening consequences, particularly in high-risk patients and in certain clinical settings. This Review examines the toxicity profiles of anti-VEGF antibodies and small-molecule inhibitors. The potential mechanisms of the adverse effects, risk factors, and the implications for selection of patients and management are discussed. Key Points Adverse effects associated with both VEGF- and VEGFR-targeting monoclonal antibodies and tyrosine kinase inhibitors are diverse, and include hypertension, arterial thromboembolic events, proteinuria, bowel perforation, reversible posterior leukoencephalopathy syndrome, wound complications and hemorrhage Risk of serious adverse events may be increased by a multitude of risk factors related to the tumor characteristics and locations, comorbidities, and prior or concurrent anticancer therapy Risk–benefit assessment is important for individual patients considering antiangiogenesis therapy In order to provide evidence-based guidance for risk identification, toxicity management and treatment adjustment for antiangiogenesis agents further research in this area is warranted