Correlation of gefitinib efficacy and detection of new EGFR mutation variants in pre-treated patients (pts) with advanced non- small cell lung cancer (NSCLC)

18062 Background: The efficacy of tyrosine kinase inhibitors (TKIs) of EGFR is associated with well characterized mutations on the exons 18, 19 and 21 of EGFR gene. Less common mutations could be detected in these exons but their relationship with the clinical efficacy of TKIs has not been established yet. Methods: Genomic DNA was extracted from microdissected formalin-fixed paraffin-embeded tumor tissue from 86 pts enrolled in a gefitinib expanded access program. Exons 18, 19 and 21 were amplified and subjected to direct sequencing. Results: Classical EGFR mutations (CM) were detected in 9 (10.4%) pts and other mutations variants (MV) in 19 (22%) pts. Eight (42.1%) MV were observed in exon 18, 3 (15.8%) in exon 19 and 8 (42.1%) in exon 21. Tumor Growth Control (TGC) was achieved in 88.9% (3PR and 5SD) pts with CM, 63% (2PR and 10SD) pts with MV and in 45.9% (3PR and 25SD) pts with wild type EGFR gene (WT). There was no clear association between the presence of EGFR MV and the sex, histology or smoking history. The median TTP was 64 weeks (range:4- 80+), 20 weeks (range:6–140) and 16 weeks (range:4–176+) in pts with CM, MV and WT, respectively. Nine (47.3%) pts with EGFR MV had a TTP >24 weeks. The median survival was 78 weeks (range:5–94+), 70 weeks (range:10–142) and 36 weeks (range:4–176+) in pts with CM, MV and WT, respectively. Three patients bearing mutations in exons 18, 19, and 21 progressed despite gefitinib treatment suggesting that these mutations could be related to resistance to gefitinib. Conclusions: EGFR mutation variants could be associated with response or resistance to TKIs but their low incidence requires their evaluation in a largest cohort of patients. No significant financial relationships to disclose.