EGFR NSCLC patients: second line therapy and beyond

In recent years, diagnosis and treatment of patients with advanced lung cancer have undergone transformational changes. The current paradigm for prescribing novel targeted therapies is based on selecting patients according to the presence of specific oncogenic abnormalities in the tumor. The efficacy of therapy targeted at a specific oncogene is convincing evidence of “oncogene addiction”, or the concept that some cancers rely on or are “addicted to” a specific gene for their survival and proliferation. The first such abnormalities discovered in lung cancer were epidermal growth factor (EGFR) kinase domain mutations; tumors with these mutations were found to be sensitive to EGFR tyrosine kinase inhibitors (TKIs). The echinoderm microtubuleassociated protein-like 4anaplastic lymphoma kinase (EML4ALK) fusion has emerged as the second most important driver oncogene in lung cancer and the first targetable fusion oncokinase to be identified in 4%-6% of lung adenocarcinomas. Crizotinib, an oral small-molecule inhibitor of ALK and c-MET receptor kinases, is now approved for treatment of ALK positive advanced non-small cell lung cancer (NSCLC), based on the results of two pivotal studies. Among EGFR or ALK mutated NSCLCs, the percentage of complete response is negligible and therefore novel, effective, safe treatments need to be tested and developed. To this end, repurposing an existing drug for treatment of NSCLC is also a worthy goal.