VEGFA and colorectal carcinoma: The landmark trials based on antiangiogenic therapy for CRC were initiated in 2004, comprising the phase II and III AVF2107 trials, which confirmed the superiority of chemotherapy (IRI, 5-FU, and leucovorin) plus bevacizumab over chemotherapy plus placebo.182 Bevacizumab is a humanized IgG monoclonal antibody targeted to VEGF-A that, according to the AVF2107 trial, improves both PFS and OS in metastatic CRC (RR: 44% vs. 34.8%; OS: 20.3 vs. 15.6 months; HR: 0.66, p < 0.001; PFS: 10.6 vs. 6.2 months; HR: 0.54; p < 0.001).