17109 Background: It was previously reported that K-ras mutations could behave as a resistance marker for response to gefitinib while EGFR mutations make NSCLC more responsive to this medication. And it is known that Asians and Westerners have different responses to gefitinib. Therefore, we are to identify the mutational status of K-ras and EGFR in the group of Chinese patients with NSCLC especially adenocarcinoma treated with gefitinib to find some helpful information. Methods: Genomic DNA was extracted from tumor specimens, including liquid nitrogen frozen tumor, paraffin blocks and fine needle biopsies from 24 patients with advanced NSCLC, who failed at least one platinum-based regimen, treated with gefitinib. Nested polymerase chain reaction products of codons 12, 13, 59, and 61 of K-ras and exon 18 through 21 of EGFR were directly sequenced at least twice. Results: Patients’ age ranges from 24 to 71 years (54.8 ± 10.2). Male/female was 14/10. Thirteen patients were smokers and 11 were non-smokers. Eighteen were adenocarcinomas, 2 were bronchioloalveolar carcinomas, 2 were squamous cell carcinomas and 2 were large cell carcinomas. The disease control (CR+PR+SD) rate was 79.2% (19/24) and the objective response (CR+PR) rate was 50.0% (12/24). No K-ras gene mutation was found in all patients. Fifteen patients (62.5%, 15/24) harbored EGFR mutations, which were delE746-A750 (8), delE746-A751 (1), delE746-A751insA (1), L861Q (1), L858R (5) and A871G (1). Two patients had double mutations (delE746-A750 and L858R). The disease control rate for wild type and mutant EGFR were 66.7% (6/9) and 86.7% (13/15), and the objective response rate were 33.3% (3/9) and 60.0% (9/15). Median time to progress (TTP) for wild type and mutant EGFR were 439 days (SE 249.8) and 367 days (SE 108.8). However, no statistically significant differences were found between these two groups regarding the response rates and TTP. Conclusions: K-ras mutation may occur at a low frequency in Chinese NSCLC groups despite the pathology, status of smoking, gender and EGFR mutations. And the relationship between the response to gefitinib and K-ras mutation might still remain to be determined at least in Chinese NSCLC. And the role of EGFR mutations in prediction of response to gefitinib should be further studied. No significant financial relationships to disclose.

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