Vascular Endothelial Growth Factor Trap in Non–Small Cell Lung Cancer

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Abstract
Several drugs currently in development target the vascular endothelial growth factor (VEGF) pathway, a validated target in the treatment of non–small cell lung cancer (NSCLC). Most clinical trial data generated to date have been with either bevacizumab, a monoclonal antibody to VEGF, or small-molecule inhibitors of VEGF receptor (VEGFR) tyrosine kinase activity (sunitinib, sorafenib, and ZD6474). VEGF Trap, an engineered soluble receptor made from extracellular domains of VEGFR1 and VEGFR2, binds to all isoforms of VEGF and to placental growth factor. VEGF Trap binds to VEGF-A and VEGF-B with markedly higher affinity than bevacizumab. The toxicities seen in phase I trials of s.c. and i.v. administration of VEGF Trap, hypertension and proteinuria, are similar to those seen with other molecules that target the VEGF pathway. In the s.c. VEGF Trap phase I trial, significant radiographic improvement was observed in a patient with heavily pretreated NSCLC. Ongoing phase I trials are evaluating combinations of VEGF Trap with platinum-based doublets and single-agent docetaxel. The activity of single-agent VEGF Trap in NSCLC is being assessed in a multicenter phase II trial.