Abstract
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.
Highlights
Non-small cell lung cancer (NSCLC), in advanced stages, has a very poor prognosis, and conventional systemic chemotherapy only results in an increase of less than one year for overall survival (OS) with a high possibility for toxicity [1,2,3]
Uncommon mutations, including E18, E20 and other complex mutations are relatively rare in NSCLC patients, with a prevalence ranging from 10%–18% [5, 6, 17, 18]
Some studies have reported sensitivities to Tyrosine kinase inhibitors (TKIs) according to epidermal growth factor receptor (EGFR) mutation types [19,20,21,22], these studies have only focused on differences between the common mutation types
Summary
Non-small cell lung cancer (NSCLC), in advanced stages, has a very poor prognosis, and conventional systemic chemotherapy only results in an increase of less than one year for overall survival (OS) with a high possibility for toxicity [1,2,3]. Clinical trials have demonstrated efficacy of TKIs for advanced EGFR-mutant NSCLC patients with these common mutations; only a small number (n) of patients with other EGFR mutations were enrolled [5, 6, 16]. The response to TKIs of NSCLC patients with uncommon mutations, including E18 and E20, and their prognoses has not been fully investigated and previous studies have found conflicting results. Uncommon mutations were associated with poorer prognoses compared with common mutations [23,24,25]. There have been limited studies comparing the prognoses of common and uncommon EGFR mutations in real-world clinical settings. The purpose of this study was to investigate outcomes of advanced lung adenocarcinomas with regard to EGFR mutation status and TKI treatment responses
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