Management of Patients with Advanced Non-Small Cell Lung Cancer: Current and Emerging Options

Systemic therapy for advanced non-small cell lung cancer (NSCLC) has evolved over the last two decades, with modest improvements in quality of life and overall survival. A plateau has been reached with traditional chemotherapy, and efforts are now being directed at developing molecularly targeted agents. To date, three such agents have been found to improve overall survival in advanced NSCLC. Erlotinib, a small-molecule inhibitor of the epidermal growth factor receptor, was approved by the US FDA in 2004 as second- or third-line treatment for advanced NSCLC. Bevacizumab, an antibody to vascular endothelial growth factor, a key mediator of angio-genesis, received approval in 2006, after a randomized trial reported a median survival of 1 year when bevacizumab was added to first-line chemotherapy. More recently, cetuximab, an antibody to the epidermal growth factor receptor, was found to improve outcome when added to chemotherapy, and FDA approval is anticipated. Several additional agents are currently being evaluated in randomized trials, with encouraging results from early studies. These and other studies are prospectively investigating predictive clinical and molecular characteristics, with the ultimate goal of individualizing therapy in advanced NSCLC.