Do We Need another Antiangiogenesis Agent for Colorectal Cancer: are Bevacizumab and Aflibercept the Same?

Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Treatment of metastatic disease has improved survival in recent years. Angiogenesis is a multistep process, and the two most potent regulatory molecules stimulating the formation of new blood vessels are vascular endothelial growth factor (VEGF) and beta fibroblast growth factor (bFGF). Bevacizumab, a recombinant monoclonal antibody that inactivates VEGF-A, was the first antiangiogenic treatment approved for use against metastatic CRC. Aflibercept, also known as VEGF-trap, is a fully humanized recombinant protein that targets VEGF-A, VEGF-B, and placental growth factor-1 (PlGF). Bevacizumab is approved for first and second-line treatment associated with chemotherapy, and aflibercept has recently been approved for second-line treatment associated with irinotecan-based chemotherapy. Their mechanism of action and the preclinical and clinical data for both treatments will be reviewed in this article, with emphasis on their developmental process and their current and future use for treating CRC.