Anti-vascular endothelial growth factor therapies at the crossroads: linifanib for non-small cell lung cancer

Activated vascular endothelial growth factor receptors (VEGFR) 1, 2 and 3, and platelet-derived growth factor receptor (PDGFR) work together to guide the microvasculature into tumor lesions, and have been shown to be involved in tumor growth, invasion and metastasis. In non-small cell lung cancer (NSCLC), tumor angiogenesis mediated by vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) is known to be associated with a poor disease free survival and poor overall survival. A randomized phase II trial was carried out to compare the efficacy/safety of three doses of linifanib with that of CBDCD + paclitaxel (PTX), as the largest and first placebo-controlled trial of linifanib for NSCLC. The result revealed modest, but not robust improvement of the progression-free and overall survival. A number of negative results and number of positive results without robust clinical benefit have been reported from trials of treatments targeting tumor angiogenesis, and anti-angiogenesis therapies seem to be at the crossroads between a prosperous future and a downhill path. Appropriate predictive markers to select right the drugs for the right patients need to be developed to obtain clinical benefit from anti-VEGF therapies.