EGFRMutations and Sensitivity to Gefitinib

Abstract

The important study by Dr. Lynch and colleagues (May 20 issue)¹ suggests that specific mutations in the epidermal growth factor receptor (EGFR) characterize a subgroup of non–small-cell lung cancers that may be highly responsive to gefitinib therapy. Do these mutations predict a greater sensitivity to chemotherapy as well? The overall objective response rate to first-line combination chemotherapy for metastatic non–small-cell lung cancer is about 20 percent.² Only tumors from a small cohort of patients who had a response to gefitinib were studied for the specific mutations, but all patients except one had also received prior chemotherapy. Although the authors describe Patient 6 as “representative” of the cohort, the percentage of other patients who previously had a response to chemotherapy is not reported. If the rate of response to first-line chemotherapy was high for the other patients in the cohort who had a response to gefitinib, the specific mutations may be predictive of either chemotherapy or gefitinib sensitivity, thus identifying a distinct subgroup of patients with non–small-cell lung cancer.