EGFR mutation, but not sex and smoking, is independently associated with favorable prognosis of gefitinib-treated patients with lung adenocarcinoma

Abstract

Objective. Intensive research has been conducted to identify factors associated with favorable clinical outcomes of gefitinib-treated patients with non-small-cell lung cancer. Epidermal growth factor receptor (EGFR) mutations have been reported as a predictive factor for favorable prognosis of gefitinib-treated patients with lung adenocarcinoma. However, its confounding with sex and smoking makes EGFR mutations' unique effect on patient survival. In this study, we analyzed a large-scale database to determine the survival impact of EGFR mutation against those of sex and smoking after gefitinib therapy. Materials and Methods. EGFR mutations in exon19 and exon21 defined as drug-sensitive EGFR mutations were examined to investigate the impact of EGFR mutation, sex, and smoking status on survival of 362 gefitinib-treated patients with lung adenocarcinoma. Results. Drug-sensitive EGFR mutations were detected in 169 patients (46.7%). The multivariate analysis including EGFR, sex and smoking status showed that drug-sensitive EGFR mutations were significantly related to prolonged overall survival (OS) (Hazard ratio = 0.48, 95% confidence interval = 0.36-0.63, P < 0.001) (PFS: Hazard ratio, 0.29, 95% confidence interval = 0.22-0.37, P < 0.001) and progression-free survival (PFS) (P < 0.001). In addition, we investigated 1) the impact of sex and smoking status according to EGFR status and 2) the impact of EGFR status according to sex and smoking status on survival. Sex and smoking status were not significantly associated with prolonged OS and PFS according to EGFR status. Drug-sensitive EGFR mutations were significantly associated with prolonged OS and PFS according to sex or smoking status. Conclusion. Our results indicated that drug-sensitive EGFR mutations were the only factor for prolonged survival of patients treated with gefitinib, suggesting that patient selection based on EGFR status for gefitinib therapy will lead to better understanding the effect of gefitinib as well as a better outcome for patients with lung adenocarcinoma. © 2009 The Japan Lung Cancer Society.