Clinical significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study

Adenocarcinoma is the most common type of non-small cell lung cancer. Some causative genomic alterations in epidermal growth factor receptor (EGFR), including deletions in exon 19 (E19 dels) and a point mutation in E21, are known to have favourable prognoses due to sensitivity to tyrosine kinase inhibitors; however, the prognoses of other uncommon mutations are unclear. This study analysed the clinical significance of EGFR mutation types in lung adenocarcinoma. We retrospectively reviewed 1,020 subjects (mean age: 66.8 years, female: 41.7%) who were diagnosed with advanced lung adenocarcinoma, had EGFR mutation data, and did not undergo surgery from five medical institutes between 2010 and 2016. Subjects were classified according to EGFR mutation status, particularly for exon-specific mutations. EGFR positivity was defined as the presence of mutation and EGFR negativity was defined as wild-type EGFR. EGFR positivity was 38.0%, with the incidence of mutations in E18, E19, E20, and E21 was 3.6%, 51.0%, 3.4%, and 42.0%, respectively. The EGFR positive group survived significantly longer than the negative group (p<0.001), and there was a significant difference in survival among the four EGFR mutation sites (p = 0.003); E19 dels were the only significant factor that lowered mortality (HR: 0.678, p = 0.002), while an E21 mutation was the prognostic factor associated with the most increased mortality (HR: 1.365, p = 0.015). Amongst EGFR positive subjects, the proportion of E19 dels in TKI-responders was significantly higher and that of E21 mutations significantly lower, compared with non-responders. In TKI treatment, mutations in E18 and E20 were not worse factors than the E21 L858R mutation. In conclusion, the presence of EGFR mutations in advanced lung adenocarcinoma can predict a good prognosis; E19 dels prospect to have a better prognosis than other mutations, while an E21 mutation is expected to increase mortality.