Update on antiangiogenic therapy in colorectal cancer: aflibercept and regorafenib

Angiogenesis plays an important role in colorectal carcinogenesis and approaches targeting the vascular growth factor receptor (VEGF) signaling such as bevacizumab yielded significant survival improvement for metastatic colorectal cancer patients. Recent evidence demonstrated the benefit of continuing angiogenic suppression after first-progression following bevacizumab-containing cytotoxic regimen though no benefit was observed with the use of bevacizumab in adjuvant setting. Aflibercept, a soluble fusion protein with high affinity for VEGF-A, -B and PlGF, administered in combination with irinotecan-containing regimen improved the survival of metastatic colorectal cancer patients in second-line setting (VELOUR trial). Regorafenib, a small molecule multikinase inhibitor against various pro-angiogenic and –proliferation targets, improved the survival of metastatic colorectal cancer patients who had progressed on all standard therapy. These developments had renewed enthusiasm in the field and the role of aflibercept and regorafenib in other treatment settings will continue to be defined by on-going and future clinical trials. As other anti-angiogenic approaches are being tested clinically, other novel non-angiogenic targets deserve to be evaluated in our effort to improve the outcome of colorectal cancer patients.