Purpose: Recently, mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) gene in non-small cell lung cancers (NSCLC) patients were reported to be correlated with response to gefitinib treatment. Because <30% of NSCLC is surgically resectable, molecular analysis will rely on routinely available non-surgical tissue samples. Here, we demonstrate the feasibility of mutation analysis in these kinds of samples and correlate mutation with clinical response and patients’ survival. Experimental Design: EGFR mutation status was assessed from the DNA of 48 formalin-fixed, paraffin-embedded specimens collected from 47 patients with histologically confirmed non-small cell lung cancer and treated with gefitinib. All these tissues were obtained by computed tomography-guided percutaneous biopsy, ultrasound-guided percutaneous biopsy, endoscopic biopsy or effusion cell blocks. Results: EGFR mutation was found in 49% of 47 patients (53% of CT-guided biopsy, 46% in ultrasound-guided biopsy, 38% from endoscopic biopsy and 57% of cell blocks). Pre-gefitinib treatment clinical features were not associated with EGFR mutation. Patients with EGFR mutations had significantly better response rate compared to non-mutation group (P< 0.001). Multivariate analysis showed that EGFR mutation (odds ratio =73; P = 0.002), performance status 0-1 (odds ratio =19; P = 0.03) and female (odds ratio=12.5; p=0.04) were independently associated with a better response rate. Cox-regression analysis showed presence of EGFR mutation (hazard ratio=0.38; p=0.036) and female (hazard ratio=0.21; p=0.001) were the independent prognostic factors for overall survival. Women had longer survival than men, but there was still a significant difference of overall survival between man with and without EGFR mutations (median 7.3 vs 2.1 months: p=0.038). Conclusions: We have demonstrated the feasibility of detecting EGFR gene mutations in a non-surgical diagnostic setting. Mutations in EGFR gene are correlated with gefitinib response and overall survival in patients with advanced NSCLC. Non-surgical tissue samples can provide serial EGFR mutation analyses in patients receiving gefitinib treatment.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]