Gefitinib in advanced non-small cell lung cancer: Clinical experience in patients of Asian origin

Background: The IRESSA Survival Evaluation in Lung cancer (ISEL) trial showed some improvement in survival which failed to reach statistical significance in the overall population and in patients with adenocarcinoma. However, gefitinib (IRESSA) treatment was associated with a significant improvement in the survival in subgroups of patients of Asian origin and never smokers. Here we review the clinical experience of gefitinib in patients of Asian origin with advanced non-small cell lung cancer (NSCLC) and discuss the evidence for the underlying biological basis for the apparent heterogeneity in clinical outcome between patients of Asian and non-Asian origin. Methods: Reports of clinical experience with gefitinib 250 mg/day in Asia were identified by searching Embase and Medline databases for publications between 1 January 2003 and 27 July 2006. Results: A large number of reports in patients of Asian origin show high objective response and disease-control rates with gefitinib treatment, with median survival >6 months and time to progression >3 months. The reports also indicate that gefitinib is generally well tolerated by patients of Asian origin and epidermal growth factor receptor (EGFR) mutations, which appear to be associated with gefitinib sensitivity, occur at a much higher rate in these patients compared with patients of non-Asian origin. These reports also indicate that a high EGFR gene copy number may be associated with their response to gefitinib. Conclusion: Gefitinib appears to be a valid, efficacious, and generally well-tolerated treatment option for patients of Asian origin with advanced NSCLC. It is possible that differences in EGFR mutation rates may underlie variations in response rates to gefitinib between Asian and non-Asian patient populations. Further exploratory analyses conducted in prospective clinical trials are required to fully determine the role of EGFR mutations, a high EGFR gene copy number and other biomarkers in determining the response to gefitinib treatment.