Increased EGFR Gene Copy Number May Predict Favorable Response to Iressa in Lung Cancer

Abstract

Patients with advanced non-small-cell lung cancer (NSCLC) whose tumor cells contain extra copies of the epidermal growth factor receptor (EGFR) gene may be more likely to respond to the drug gefitinib (Iressa), and this high gene copy number may be an effective predictor of gefitinib efficacy, according to a new study in the May 4, 2005 issue of the Journal of the National Cancer Institute. EGFR inhibitors have a significant effect in a sub-population of patients with NSCLC. However, the problem that physicians face is how to select the group of patients who will benefit.NSCLC is the leading cause of death worldwide. In patients with advanced disease, chemotherapy produces only modest survival benefits. However, about 12 to 27 percent of advanced NSCLC patients respond to tyrosine kinase inhibitors, such as gefitinib and erlotinib (Tarceva). Methods to predict which patients are most likely to respond to these drugs are under development.To investigate possible predictive markers for gefitinib efficacy, Fred R. Hirsch, M.D., Ph.D., of the University of Colorado Cancer Center in Aurora, and colleagues evaluated EGFR status, gene copy number, and protein expression and Akt activation status in 102 patients with advanced NSCLC."Cancer research is leading us in a direction where we can customize cancer therapy to treat every patient based on the biological profile of their tumor," explained Hirsch. "The results we found in this study are an example of how useful it is for us to profile the tumor to provide therapies that the patients are more likely to respond to."Amplification or high copy number of the EGFR gene (33 of 102 patients) was associated with a better response rate (36% versus 3%), disease control rate (67% versus 26%), time to progression (9.0 months versus 2.5 months), and survival (18.7 months versus 7.0 months) compared with patients with a low number of or no extra copies of the EGFR gene. A similar association was found for patients with high protein expression (58 of 98 patients) compared with patients with low protein expression. EGFR mutations (15 of 89 patients) were also associated with a better response rate and time to progression. However, further statistical analysis revealed that only high EGFR gene copy number is associated with better survival."In conclusion, results from this study demonstrate that gefitinib is most effective in advanced NSCLC patients with high EGFR gene copy number, expression, or EGFR mutations. Because only high EGFR gene copy number was associated with prolonged survival… and because [fluorescence in situ hybridization (FISH)] is a readily available clinical test, the EGFR FISH analysis represents an ideal test for selecting candidate NSCLC patients for gefitinib therapy," the authors write.The University of Colorado Cancer Center, located in Denver at the University of Colorado Health Sciences Center, is the only National Cancer Institute-designated comprehensive cancer center in the Rocky Mountain Region. Its four-part mission is excellence in cancer treatment, research, education and prevention. For more information, visit the Web site at www.uccc.info.