TKIs in NSCLC: The down of a new era?

The understanding of the molecular pathology of carcinogenesis in non-small cell lung cancer (NSCLC) has led to the development of targeted agents. One of the most profoundly investigated pathways is that of the epidermal growth factor (EGF) and its receptor (EGFR). In our days we have two types of inhibitors of EGFR, one being the extra-membrane and the other, the intra-cellular tyrosine kinase domain (EGFR-TKIs). The initial studies with EGFR-TKIs, gefitib and erlotinib, had demonstrated that a small proportion of unselected patients with NSCLC showed a great response to these agents. It took more than 5 years to understand the reason for this response. A large and confusing body of small or retrospective molecular studies were published in order to evaluate if the EGFR expression by immunohistochemistry (IHC) or the EGFR copy number by in situ hymbidiazation (FISH) can predict response to the new agents before actually concluding that the EGFR gene mutation status is the predominate predictive marker (1). This delay could underscore the need for quick and total shift in the design of the lung cancer trials.