Abstract 4849: An association between genetic variant in Epidermal Growth Factor (EGF) gene and survival benefit from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in never smokers with advanced adenocarcinoma of the lung.

Abstract

Abstract Background EGFR mutations are strong predictors for efficacy to EGFR-TKIs in non-small cell lung cancer (NSCLC). However, it is unknown whether inherited genetic variants can influence the EGFR-TKI efficacy in patients harboring EGFR mutations. Methods We genotyped 271,817 single-nucleotide polymorphisms (SNP) in 348 advanced NSCLC patients who received chemotherapy. Seventeen top survival-related SNPs were identified using cut-off minimum P-value of <5.0 x 10−5 in at least 70% of 1000 bootstrap samples. Among the 17 genes, we focused on whether SNPs in the EGF gene have predictive value for survival benefit from EGFR-TKIs in 215 never smokers with advanced adenocarcinoma of the lung, which were selected as EGFR mutation-enriched patients, receiving EGFR-TKI treatment during the disease course. Results The survival benefit by treatment with EGFR-TKIs was different between patients with common and variant genotypes of rs11098063 at the 4q25: EGF gene [hazard ratio (HR) of ever to never use of EGFR-TKIs, 0.72 (95% CI, 0.42-1.22) in CC genotype vs. 0.27 (95% CI, 0.15-0.50) in CT/TT genotype; interaction of SNP*EGFR-TKIs, P = 0.075] in Cox proportional hazard regression model adjusted for known prognostic factors. In the CT/TT group (n= 89), there was a significant improvement in survival with EGFR-TKIs [never vs. ever use of EGFR-TKIs; median overall survival (OS), 16 (95% CI, 12-21) vs. 37 (95% CI, 31-42) months; log-rank test, P < 0.001]. However, the CC group (n= 126) did not show a significant difference in survival according to use of EGFR-TKIs [never vs. ever use of EGFR-TKIs; median OS, 14 (95% CI, 9-18) vs. 25 (95% CI, 23-27) months; log-rank test, P = 0.082]. On the other hand, the SNP of the EGF gene was not associated with response rate or progression-free survival of EGFR-TKIs. Conclusions These results suggested the genetic variants at the EGF gene might contribute to the survival difference associated with EGFR-TKI treatment in EGFR mutation-enriched patients. Citation Format: Youngjoo Lee, Kyong-Ah Yoon, Jin Soo Lee. An association between genetic variant in Epidermal Growth Factor (EGF) gene and survival benefit from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in never smokers with advanced adenocarcinoma of the lung. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4849. doi:10.1158/1538-7445.AM2013-4849