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 issue of the Journal of the National Cancer Institute.
NSCLC is the leading cause of cancer death worldwide. In patients with advanced disease, chemotherapy produces only modest survival benefits. However, about 12% to 27% 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.
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 versus 2.5 months), and survival (18.7 versus 7.0 months) compared with patients with a low number 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.