Although the responses we see with a targeted therapy like the epidermal growth factor receptor (EGFR) oral tyrosine kinase inhibitors (TKIs) for patients with the precise target, an activating mutation in the EGFR gene, has redefined our hopes and expectations about what is possible to achieve for at least some patients with advanced non-small cell lung cancer (NSCLC), nearly all of these patients develop a resistance to these agents at some point months or years after often having a very significant response to one of these agents.