Effectiveness of tyrosine kinase inhibitors on uncommon E709X epidermal growth factor receptor mutations in non-small-cell lung cancer

Background: Clinical features of epidermal growth factor receptor (EGFR) mutations: L858R, deletions in exon 19, T790M, insertions in exon 20, G719X, and L861X in non-small-cell lung cancer (NSCLC) are well-known. The clinical significance of other uncommon EGFR mutations, such as E709X, is not well understood. This study aimed to improve the understanding of E709X, and the clinical response to tyrosine kinase inhibitors (TKIs) of NSCLC patients with such an uncommon mutation. Methods: Specimens from 3,146 patients were tested for EGFR mutations. We surveyed the clinical data and the effectiveness of TKI treatment in NSCLC patients with EGFR mutations E709X. Results: Of the 3,146 patients, 1,689 (53.7%) had EGFR mutations. This included 726 patients with deletions in exon 19, 733 patients with L858R, and 230 (13.6%) patients with other EGFR mutations. In the 230 patients who had mutations other than single deletion in exon 19 or single L858R in exon 21, 25 (1.5%) patients had the uncommon E709X mutations. Twenty patients had complex E709X mutations and five had single E709X mutation: delE709-T710insD. Of these 25 patients, 18 received either gefitinib or erlotinib treatment. The response rate of TKIs treatment was 50.0%, and the median progression-free survival was 6.2 months. All 5 patients who had delE709-T710insD were non-responders to TKI treatments. Conclusion: E709X EGFR mutations constituted a small part of the whole group of EGFR mutations. Most patients had complex mutations. The mutation delE709-T710insD was a single mutation and was not associated with good response to TKI treatment.