Predictors of gefitinib outcomes in advanced non-small cell lung cancer (NSCLC): study of a comprehensive panel of molecular markers.

A number of different clinical characteristics and molecular markers related to epidermal growth factor receptor (EGFR) activation have been reported to singly correlate with therapeutic activity of EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). This study was designed to evaluate the predictive value on gefitinib outcomes of a comprehensive panel of molecular parameters in advanced NSCLC patients. EGFR and K-ras mutations were detected by direct sequencing on tumor DNA from paraffin embedded samples. EGFR and HER2 gene copy number was assessed by FISH. EGFR protein expression was quantified by immunohistochemistry. EGFR gene intron 1 polymorphism was assessed on genomic DNA isolated from venous whole blood samples. Ninety-one patients were prospectively enrolled and the overall gefitinib response rate was 18.7% (2 complete and 15 partial responses). Sex (p=0.005), non-smoking status (p=0.010), skin toxicity (p=0.020), EGFR gene mutations (p