P1.01-38 Clinical Significance According to EGFR Mutation Subtypes in Lung Adenocarcinoma: Korean Multicenter Experience

Abstract

Adenocarcinoma is the most common type of non-small cell lung cancer causing genetic mutations. The most common gene mutations associated with EGFR receptors are deletion at exon 19 and point mutation at exon 21, L858R. However, other uncommon mutations cover 10 to 18% of all EGFR mutations. Mutations in exon 18 and 20 are important in incidence among uncommon mutations. We aimed to analyze the clinical significance according to EGFR mutation subtypes in lung adenocarcinoma. Data were collected from 5 university hospitals in Seoul and Gyeonggi province of Korea. During the period from 2010 to 2016, patients of lung adenocarcinoma of stage 3 to 4 who were not treated surgically and examined for EGFR mutation were enrolled. The total subjects were 1021 persons. Patients were retrospectively analyzed for clinical features by subtypes of EGFR mutation. EGFR positivity was 38.1%: mutation positive group was significantly lower in males and smokers compared to mutation negative group, while in mutation positive group the proportion of patients receiving traditional chemotherapy or EGFR targeted therapy was significantly higher and also percentage of stage IV were significantly more than that of stage III. Among EGFR positivity, the incidence of mutations in exon 18, 19, 20, and 21 were 3.6%, 51.2%, 3.3%, and 41.9%, respectively. Among the four subtypes, the age was relatively low at exon 19 mutation (p=0.006), while the proportion of smokers was particularly high at exon 20 mutation (p=0.016). EGFR positive group survived significantly longer than the negative group (p<0.001), and there was a significant difference in survival among the four subtypes of EGFR positive group (p=0.004): mutation in exon 19 showed a better survival probability compared to the other subtypes (p<0.001), whereas mutation in exon 21 showed a poorer prognosis (p=0.006). Univariate and multivariate analysis showed that mutation in exon 19 was the only significant factor that lowered the mortality rate (HR:0.415, p=0.001) and mutations in exon 18, 20 and 21 were not significant. In EGFR positivity, TKI non-responder showed significantly higher proportion of exon 21 mutation, compared to TKI-responder (p<0.05). Presenting mutation of exon 19 in advanced lung adenocarcinoma prospects better survival than other EGFR mutations. Unlike the previous reports, mutation in exon 18 or 20 was not a worse factor than mutation in exon 21.