Current and emerging therapies for patients with advanced non-small-cell lung cancer

Purpose. To review recent clinical trials that have examined new options for the treatment of non-small-cell lung cancer (NSCLC) and to review the importance of tumor histology and genetics in the selection of therapy. Summary. Targeted biological agents have been evaluated for use in patients with NSCLC. In a recent study, treatment with cetuximab plus chemotherapy led to significant improvement in overall survival (OS) in patients with advanced NSCLC. A Phase III, noninferiority, randomized study evaluating first-line therapy in patients with stage IIIb or IV NSCLC demonstrated that the combination of cisplatin and pemetrexed was noninferior to cisplatin and gemcitabine in improving OS and other clinical outcomes. In this study, the combination of pemetrexed and cisplatin was effective in patients with nonsquamous disease, whereas the combination of cisplatin and gemcitabine was effective in improving progression-free survival (PFS) in patients with squamous cell carcinoma. Clinical trials of maintenance therapy presented at the 2009 annual meeting of the American Society of Clinical Oncology reported significant benefit of pemetrexed in patients with nonsquamous tumor histology, and of erlotinib in patients with squamous and nonsquamous histology. For second-line therapy, studies of the investigational tyrosine kinase inhibitor, vandetanib, failed to demonstrate improved OS with vandetanib in combination with docetaxel or pemetrexed, or in direct comparison with erlotinib. In another study, the addition of bevacizumab to erlotinib for second-line treatment of NSCLC did not result in greater OS than erlotinib alone. Conclusion. New treatment strategies are needed to improve clinical outcomes for patients with advanced NSCLC. The introduction of new agents with improved tolerability profiles has led to interest in long-term maintenance therapy in this patient population. Clinical trials suggest that tumor histology and genetics should be considered when selecting treatments for these patients.