Journal Article

Aflibercept: A Review in Metastatic Colorectal Cancer

McKeage, Kate, Syed, Yahiya Y.

2015

Overview

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.

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Adis Drug Evaluation / Angiogenesis / Angiogenesis Inhibitors - adverse effects / Angiogenesis Inhibitors - pharmacokinetics / Angiogenesis Inhibitors - therapeutic use / Animals / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Apoptosis / Cancer therapies / Chemotherapy / Colorectal cancer / Colorectal Neoplasms - blood supply / Colorectal Neoplasms - drug therapy / Colorectal Neoplasms - metabolism / Colorectal Neoplasms - mortality / Colorectal Neoplasms - pathology / Disease Progression / Disease-Free Survival / Humans / Hypoxia / Internal Medicine / Medical prognosis / Medicine / Medicine & Public Health / Metastasis / Neoplasm Metastasis / Neovascularization, Pathologic / Pharmacology/Toxicology / Pharmacotherapy / Placenta Growth Factor / Pregnancy Proteins - antagonists & inhibitors / Pregnancy Proteins - metabolism / Proteins / Receptors, Vascular Endothelial Growth Factor - adverse effects / Receptors, Vascular Endothelial Growth Factor - pharmacokinetics / Receptors, Vascular Endothelial Growth Factor - therapeutic use / Recombinant Fusion Proteins - adverse effects / Recombinant Fusion Proteins - pharmacokinetics / Recombinant Fusion Proteins - therapeutic use / Risk Factors / Signal Transduction - drug effects / Survival Analysis / Treatment Outcome / Tumors / Vascular endothelial growth factor / Vascular Endothelial Growth Factor A - antagonists & inhibitors / Vascular Endothelial Growth Factor A - metabolism / Vascular Endothelial Growth Factor B - antagonists & inhibitors / Vascular Endothelial Growth Factor B - metabolism