Epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer: Impact of primary or secondary mutations

The discovery of mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) and the positive results of the National Cancer Institute of Canada Clinical Trials Group BR.21 phase III, randomized, placebo-controlled trial of erlotinib in patients with advanced-stage non-small-cell lung cancer that had failed to respond to first- or second-line chemotherapy provides now treatment options for patients with lung cancer and now insights into the pathophysiology of this malignancy. The similarity in patient characteristics significantly associated with EGFR mutations and in those who responded to therapy In BR.21 led to the hypothesis that EGFR mutation status can be used as a predictive marker for response and survival benefit in patients treated with the EGFR TK inhibitors erlotinib and gefitinib. This review summarizes the available data to date on the frequency and type of EGFR TK domain mutations and their association with clinical features, response, and survival outcome of patients treated with erlotinib and gefitinib.