A preclinical and clinical review of aflibercept for the management of cancer

Aflibercept, also known as vascular endothelial growth factor (VEGF)–Trap, is a recombinant, decoy receptor fusion protein, rationally designed to block angiogenesis by targeting not only all forms of VEGF-A, but also VEGF-B and placental growth factor. It inhibits VEGF-induced angiogenesis in preclinical models. In tumor models, aflibercept is associated with the reduction of tumor vasculature and size, and the inhibition of ascites formation. Clinical studies are investigating the use of aflibercept alone and in combination with other antineoplastic therapies for the treatment of various cancers. Phase I and II studies have provided proof of principle, and support the continuing clinical investigation of aflibercept. Results from the phase III study, VITAL, of aflibercept in the second-line setting in patients with advanced non-small cell lung cancer [NCT00532155] demonstrated efficacy in progression-free survival and overall objective response rate, but overall survival was not significantly improved. A full report awaits publication. The Phase III VANILLA trial in metastatic pancreatic cancer [NCT00574275] showed no improvement in overall survival. Most recently, the phase III VELOUR study [NCT00561470] of aflibercept plus FOLFIRI compared with placebo plus FOLFIRI in patients with metastatic colorectal cancer following failure of an oxaliplatin regimen showed significant improvements in overall survival, progression-free survival, and response rate and the complete results have been submitted to a peer-reviewed journal. This review summarizes preclinical and clinical data for aflibercept and discusses future directions and clinical trials for this agent.