Biological Agents in Non-small Cell Lung Cancer: A Review of Recent Advances and Clinical Results with a Focus on Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor

Despite improvements in conventional therapy for non-small cell lung cancer (NSCLC) with surgery, radiotherapy, and cytotoxic chemotherapy, survival remains poor and further improvements are needed. Targeted therapy with biologic agents offers a novel treatment strategy. In the first-line treatment of advanced disease, the most promising results to date have been reported with bevacizumab [an antivascular endothelial growth factor (anti-VEGF) antibody] plus chemotherapy, with significant improvement in survival, compared with chemotherapy alone, in a selected population of patients with nonsquamous histology. Trials incorporating epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors with chemotherapy failed to produce a survival benefit. Nevertheless, cetuximab (an anti-EGFR IgG1 monoclonal antibody) plus chemotherapy has shown promising results in initial studies and continues to be evaluated in larger trials. The benefits of EGFR and VEGF inhibitors in advanced disease have propelled them into evaluation in early stages of NSCLC. Integration of these agents into bi- and tri-modality treatments is currently under investigation in these settings. Finally, emerging data combining EGFR and VEGF inhibitors suggest that multiple pathway inhibition may be more effective than targeting a single pathway.