Association between gene mutant protein expression and T790M mutation after first-generation EGFR-TKI treatment resistance: a retrospective, single-arm clinical study.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is an important treatment for lung adenocarcinoma patients with gene mutations. The purpose of this study was to review the efficacy of first-generation EGFR-TKIs and the incidence of T790M after first-generation TKI resistance in stage IV lung adenocarcinoma patients with positive gene mutation expression associated with EGFR mutant protein.

Methods: Tumor tissues were collected from stage IV lung adenocarcinoma patients with gene mutation who received first-generation EGFR-TKI targeted therapy. Patients were followed up through outpatient and inpatient systems. Immunohistochemistry was used to detect the expression of corresponding EGFR mutant protein in tumor tissues. The incidence of T790M mutation after first-generation TKI resistance and the correlation between the mutant protein and progression-free survival (PFS) after first-generation TKI treatment were investigated.

Results: T790M mutation rates were 37.93% (11/29) and 42.50% (17/40) in the mutation groups, respectively, after first-generation TKI treatment for drug resistance. In patients with exon 19 deletion, T790M mutations were found in 63.64% (7/11) of patients with positive protein expression and 22.22% (4/18) of patients with negative protein expression (P0.026; χ=4.974). The mutation rate of T790M after drug resistance in patients with L858R mutation was 53.57% (15/28) and 16.67% (2/12) in the protein expression-positive and negative groups, respectively (χ=4.682, P0.030). The variations were statistically significant.

Conclusions: After resistance to the first-generation EGFR-TKI treatment, the occurrence of T790M mutation may be related to the expression of EGFR mutant protein in patients with gene mutation.