Significance of Polar Charged Amino Acids in Compound Mutations in EGFR-mutated Patients Treated With First-line Afatinib

Abstract

Background/Aim: Next-generation sequencing (NGS) has recently made it possible to investigate polar charged amino acids in compound mutations in the epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). Several preclinical studies have suggested the involvement of polar charged amino acids in the treatment of EGFR mutations and EGFR-tyrosine kinase inhibitors (TKIs). With this background, a retrospective study was conducted aiming to clarify the prognostic significance of these amino acids in complex mutations in NSCLC patients with common EGFR mutations. Patients and Methods: EGFR gene mutations were investigated using nonoverlapping integrated read sequencing system (NOIR-SS) in pathological specimens of 20 EGFR-mutated NSCLC patients. For clinical information, the medical records were retrospectively investigated. We investigated prognostic significance of these amino acids in compound mutations in progression free survival (PFS) and overall survival (OS) in patients treated with first-line afatinib. Results: Among the 20 patients examined, 5 patients had polar charged amino acids in compound mutations and 15 had not. There were no statistically significant differences in the clinical background factors examined in these two groups of patients. In uni- and multivariate analysis, ‘poor performance status’ and ‘polar charged amino acids in compound mutations’ were significant favorable factors in OS. Conclusion: Patients with ‘polar charged amino acids in compound mutations’ might have favorable prognosis than those without them. Detailed examination of EGFR gene information might contribute to the understanding of TKI response duration.