EGFR tyrosine kinase inhibitors for the treatment of NSCLC in East Asia: present and future.

Treatment with one of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib or erlotinib has become an additional option for patients with non-small cell lung cancer (NSCLC). Further investigation clearly demonstrated that a subset of patients show a better response to these agents than the overall patient population: individuals with adenocarcinoma histology, females, never-smokers and those of East Asian origin. The ISEL and BR21 studies showed that East Asian patients had significantly longer survival compared with the total study population after EGFR-TKI treatment. The increased response to EGFR-TKIs observed in East Asian patients can likely be attributed to the higher prevalence of activating EGFR mutations found in these individuals. Data from several studies in Japan, Korea, Taiwan and China support this, showing a high occurrence of activating mutations. Furthermore, in prospective studies of gefitinib in these populations, sensitive activating mutations (deletions in exon 19 or L858R) are associated with high overall response and disease control rates. Within East Asian patients, predictors of response to gefitinib include female sex, adenocarcinoma histology, no smoking history and receiving gefitinib first-line, although there may be an interaction between these factors. All patients eventually develop acquired resistance to the currently available EGFR TKIs. In addition, the presence of EGFR mutations is a useful tool to determine NSCLC patients' prognosis; some studies suggested that this may apply if patients are receiving first-line chemotherapy, not only if they are receiving EGFR-TKIs.