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A7335 - Stratifying Somatic EGFR Mutation Profiles for Detection of Drug Resistant Mutations in NSCLC
Author Block: M. Sachdeva, M. Bilello, M. W. Peterson, D. Upadhyay; Pulmonary and Critical Care, University of California, San Francisco, Fresno, CA, United States.
Rationale:With increasing discoveries of drug resistant mutations in epidermal growth factor receptor (EGFR) gene, identification and stratification of specific somatic EGFR mutation profiles has become critically important in the selection of appropriate treatment in patients with NSCLC (Non-Small Cell Lung cancer). EGFR mutations have a higher prevalence in non-smoker females with NSCLC. Our study investigates the prevalence of somatic EGFR mutations and drug resistant mutations in NSCLC.Methods:We analyzed the tumor gene mutation profiles from tumor biopsy tissue in patients presenting with newly diagnosed NSCLC to our Lung Nodule Program. To determine the association between gender, ethnicity, tobacco use and mutation status we used the Pearson’s χ2 test.Results:In this study of 170 patients with non-small cell lung cancer, 25 had an EGFR mutation. Of these 25 with an EGFR mutation 36% were male and 64% female. 32% were smokers and 68% nonsmokers. Of the 25 with EGFR mutations 44% of males were smokers and 56% non-smokers and in females 25% were smokers and 75% non-smokers. The EGFR patient database was further stratified for site mutations of EGFR within gender vs. smoking status. Of the EGFR mutations in male smokers, 33% were exon 19 deletions and 67% were other EGFR mutations. Of the EGFR mutations in male non-smokers, 20% were exon 21 deletions and 80% were other EGFR mutations. Of the EGFR mutations in female smokers, 29% were exon 19 deletions while 71% were other EGFR mutations. Of the EGFR mutations in female nonsmokers, 9.5% were exon 19 deletions, 9.5% were exon 20 insertions, 9.5% were exon 21 deletions, 61.9% were other EGFR mutations, and 9.5% were drug resistant T790M mutations. When men and women with an EGFR mutation were stratified for all EGFR site mutations, it was found that 15% were Exon 19 deletions, 5% were exon 20 insertions, 8% were exon 21 deletions, 67% were other EGFR site mutations, and 5% were T790M mutations. No Exon 18 site mutations were found.Conclusion:Appropriate treatment of NSCLC patients with EGFR mutation has shown to improve progression-free survival. Our study shows that EGFR mutations are highly prevalent in non-smoking females with NSCLC. This data is invaluable in expediting the appropriate treatment of patients with NSCLC with EGFR mutations and drug resistant mutations.