Adverse Events Associated With Antiangiogenic Agents in Combination With Cytotoxic Chemotherapy in Metastatic Colorectal Cancer and Their Management

Colorectal cancer (CRC) is the third most common cancer in men and women, and, despite advances in detection and treatment that result in a steadily decreasing incidence and mortality, remains a leading cause of death. The 5-year survival rate of persons with metastatic CRC (mCRC) is only 12%. With the recognition of vascularity as an important factor in tumor proliferation and growth, targeting angiogenesis pathways has been a major focus of research. The addition of bevacizumab, an inhibitor of the vascular endothelial growth factor (VEGF) pathway, to cytotoxic chemotherapy has improved response rates and survival of patients with mCRC. Aflibercept, a potent new multiple angiogenic factor trap that prevents not only VEGF-A but also VEGF-B and placental growth factor from activating their native receptors, has demonstrated efficacy in previously treated patients with mCRC. Phase I/II clinical trials and, more recently, a phase III clinical trial, have demonstrated effective antiangiogenic and cytotoxic activity with acceptable safety and tolerability. As is the case with bevacizumab, the optimal use of aflibercept requires appropriate management of the associated anti-VEGF adverse events and those associated with its use in combination with chemotherapy. These adverse events have previously been observed and are generally manageable with appropriate therapeutic intervention.