P1.07-024 EGFR Mutations in Small Cell Lung Cancer (SCLC): Genetic Heterogeneity and Prognostic Impact: Topic: Molecular Changes

EGFR mutations in SCLC were first reported in cases of lung adenocarcinoma which transformed to SCLC after TKI treatment and such mutation was speculated to be a TKI resistance mechanism. Recently case reports and high throughput sequencing in a small number of samples suggested that EGFR mutations do exist in de novo SCLC. But the genetic and clinical characteristics have not been studied in large number of samples. This study aims to conduct a large scale survey of the EGFR mutations among Chinese SCLC patients, and to analyze the genetic and clinical characteristics of such mutations. Mutation status in exon 18-21 of EGFR was assessed by dideoxy-sequencing in 565 SCLC tumors treated in Zhejiang Cancer Hospital, Hangzhou, China from 2009 to 2014 and correlated with clinical parameters. Chi-square tests were used to show the correlation of clinic variables with EGFR mutation. Survival analysis was performed using the Kaplan-Meier method. 40 instances of EGFR mutation are detected in 565 clinical samples. The mutation rate is 7.1%. Besides classic mutations E19 deletion (n=3) and E21 L858R (n=3), the rest of the mutations detected are atypical including E18 (G719D/S, G696R, S695N/D, N700D, I715F, L688F, P694L), E19(K757N, A755V, V742I, E736K, N756Y, E749K, P753L, A755T), E20 (T790M, H773R, S768R/N, R776H/C, G796D, D807N, R803W/Q, Y813C, G810S, A763T, G779D, Q791R, C781Y, N771S), E21(L858V, G874R, K867E). Among the EGFR mutation positive patients, 27.5% (11/40) are non-smokers, higher than the EGFR negative group (16.4%, 86/525). But it is not statistically significant (p=0.129). And EGFR mutation is not correlated with sex (female vs male), age (≥65y vs <65y) or clinical stages (limited stage vs extensive stage). After matching the treatment history of the EGFR mutation positive and negative patients (excluding patients who were not treated, only treated by traditional Chinese medicine or one cycle chemotherapy or biological therapy, treatment unknown), univariate analysis shows that the EGFR mutation positive patients have better overall survival than the EGFR negative group, with medium OS of 24.433m±4.864m vs 14.00m±0.838m respectively (p=0.018). COX regression analysis suggests that limited stage (HR=2.610), <65 years (HR=1.476) and EGFR mutation (HR=0.587, p=0. 0.039) were independently predictive of better OS. Among the de novo SCLC patients diagnosed, there exists a group harboring EGFR mutations, most of which are non-classic mutations. After matching the treatment history of patients, analysis reveals that EGFR mutations are predictive of better OS.