7006 Background: Gefitinib, a small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase leads to major responses in ≤19% of pts; symptoms improve in nearly half (IDEAL I & 2). When combined with systemic chemotherapy, no therapeutic gain was seen compared to chemotherapy alone (INTACT I & II). Somatic activating mutations in the EGFR-TK domain (exons 18–21) have been found in pts with a dramatic, rapid response to gefitinib (Lynch et al, Paez et al, Pao, et al). Methods: Tumor samples were obtained from patients enrolled on the IDEAL studies (monotherapy for previously treated patients) and INTACT studies (randomized trials of chemotherapy +/- gefitinib in untreated advanced stage patients). Using standard sequencing protocols we sequenced exons 18–21 of EGFR TK domain. Selected samples were analyzed for ras and p53 mutations. Correlations were made between mutational status, therapies and outcome measures including tumor response and survival. Results: Among 416 IDEAL patients, 119...