Resistance patterns of non-small cell lung cancer treated with third-generation epidermal growth factor receptor-tyrosine kinase inhibitors

The third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the preferred therapy for patients with EGFR mutant non-small cell lung cancer (NSCLC); however, the therapy faces resistance challenges. We aimed to clarify the resistance patterns of EGFR-TKIs in patients with EGFR mutant NSCLC. In this retrospective study, we analyzed 104 patients with advanced EGFR mutant NSCLC who experienced treatment failure of third-generation EGFR-TKIs. Resistance models were classified as 1) original site failure (OF), distant site failure (DF), and combined failure (ODF) based on the failure site or 2) oligo-progression (OP) and non-oligoprogression based on the disease progression (PD) pattern. Among the patients, 58.7% (n = 61 of 104) developed OF, while 25 (24.0%) and 18 (17.3%) developed DF and ODF, respectively. A high OP rate (76.9%, n = 80) was observed, with primary progression accounting for 30.8%. OF was related to sex (odds ratio = 3.961, 95% confidence interval: 1.629-9.631, P = 0.002). Over 50% of patients with third-generation EGFR-TKI treatment failure developed OF. Sex, central nervous system metastases, and disease stage influenced the resistance patterns of the EGFR-TKI therapy.