Treatment

Personalized Therapy for Non-Small Cell Lung Cancer

This proof-of-principle pilot project investigates the comparative effectiveness of advanced NSCLC treatments guided by EGFR and KRAS testing and histology to standard, empiric treatment. In 2009, 45% of all newly diagnosed lung cancer cases will be advanced stage (stage IV or “wet” IIIB) non-small cell carcinoma (NSCLC). Standard treatment involves empiric, relatively toxic therapy given with little distinction between histologic subtypes and virtually no input based on molecular typing. However, developments in cancer genomics over the last five years suggest that both pathologic analysis and molecular typing may be important in determining appropriate therapy for patients with NSCLC. For example, bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, in combination with standard chemotherapy improves survival in non-squamous histology, but is contraindicated in patients with squamous cell carcinoma. Erlotinib, a prototypical EGFR inhibitor, yields modest improvements in survival compared to placebo in the second and third line setting but response appears to be predicted by EGFR and KRAS mutation status. This observation is being confirmed in several prospective clinical trials.