title: Aflibercept: A Review in Metastatic Colorectal Cancer.
abstract: Aflibercept is a recombinant fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor (VEGF), a key regulator of angiogenesis. It binds to all isoforms of VEGF-A as well as VEGF-B and placental growth factor, and, thus, prevents them from binding to and activating their cognate receptors. In the USA and EU, intravenously administered aflibercept in combination with an infusion of leucovorin, fluorouracil and irinotecan (FOLFIRI) is approved for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed after treatment with an oxaliplatin-containing regimen. The efficacy of aflibercept in this indication was assessed in a multinational, pivotal phase 3 trial (VELOUR), in which the approved regimen of aflibercept 4 mg/kg every 2 weeks plus FOLFIRI significantly prolonged median overall survival by 1.44 months compared with FOLFIRI alone (primary endpoint). The addition of aflibercept also significantly prolonged progression-free survival and significantly increased the objective response rate compared with FOLFIRI alone. Addition of aflibercept to FOLFIRI was associated with anti-VEGF-related adverse events and an increased incidence of FOLFIRI-related adverse events, but the tolerability of the combination was generally acceptable in this pre-treated population. The most common grade 3 or 4 adverse events with aflibercept plus FOLFIRI included neutropenia, diarrhoea and hypertension. In conclusion, aflibercept plus FOLFIRI is a useful treatment option for patients with metastatic colorectal cancer previously treated with an oxaliplatin-containing regimen, with or without bevacizumab.
authors.affiliation: Springer, Private Bag 65901, Mairangi Bay 0754, Auckland, New Zealand, demail@springer.com.
authors.forename: Yahiya Y
authors.initials: YY
authors.lastname: Syed
authors.forename: Kate
authors.initials: K
authors.lastname: McKeage
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism; D042561:Vascular Endothelial Growth Factor B / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; C467485:VEGFB protein, human; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D000072483:Placenta Growth Factor; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor