Complex decisions for first-line and maintenance treatment of advanced wild-type non-small cell lung cancer

Until recently, the first-line treatment of advanced non-small cell lung cancer (NSCLC) required minimal clinical decision making. Patients who were eligible for chemotherapy received a platinum-based doublet, and 5-year survival rates were poor. With the advent of molecularly targeted agents and better tolerated chemotherapies--namely, bevacizumab, erlotinib, and pemetrexed--new therapeutic opportunities have emerged. Some of the strategies that have proven to be successful for the treatment of patients with NSCLC are targeting of the vascular endothelial growth factor, use of maintenance chemotherapy for patients without progression of disease after initial therapy, and tailoring of cytotoxic agents specific to the histology of an individual patient's cancer. Each approach has been independently shown to improve overall survival, but integrating the data from a number of complicated trials into the "best" approach for patients remains challenging. This review attempts to address three fundamental questions clinicians face in choosing first-line and maintenance treatment for advanced NSCLC, particularly nonsquamous histology: Is pemetrexed or a taxane agent better for combination with platinum therapy? Should bevacizumab be used, and is it beneficial when added to pemetrexed chemotherapy? When is maintenance therapy indicated, and which agent is best?