Background:EGFR mutations are predictive of gefitinib efficacy in non-small-cell lung cancer. Secondary T790M mutation is one of the causes of gefitinib resistance.

Methods: We analyzed exons 18-21 of EGFR from cancer before gefitinib treatment and after disease progression from 23 patients with partial response to gefitinib. We also analyzed 9 patients with stable disease as the maximal response after disease progressed.

Results: Inthe sensitive group, 22 were non-smoker, and 21 were female. Median follow-up from the start of gefitinib was 18 months. After disease progression, secondary T790M mutation was detected in13 patients; 4 with deletion in exon 19, 9 with L858R. Patients without T790M mutation had better progression-free survival than those with T790M mutation (median 9.2 months and 6.8 months respectively, p=0.045). There was no difference in overall survival between patients with and without secondary T790M mutation. No secondary T790M was found in 9 patients of stable disease group. Secondary T790M mutation occurs in gefitinib sensitive patients, but not in patients of stable disease. T790M mutation rate after gefitinib resistance was 56% in patients with tumor response to gefitinib. Those with T790M mutation had shorter progression-free survival.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA