학술논문

Clinical outcomes of advanced NSCLC patients with different EGFR exon 19 deletion subtypes treated with first‐line tyrosine kinase inhibitors: A single‐center ambispective cohort study
Document Type
article
Source
Thoracic Cancer, Vol 14, Iss 31, Pp 3147-3160 (2023)
Subject
EGFR exon 19 deletion subtypes
non‐small cell lung cancer
overall survival
progression‐free survival
tyrosine kinase inhibitor
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Language
English
ISSN
1759-7714
1759-7706
Abstract
Abstract Background Clinical significance of various subtypes of epidermal growth factor receptor (EGFR) exon 19 deletion (ex19del) mutation in non‐small cell lung cancer (NSCLC) remains unclear. Methods We analyzed EGFR ex19del subtypes in NSCLC patients receiving first‐line tyrosine kinase inhibitor (TKI) therapy at our center (January 2018–June 2022) and correlated them with median progression‐free survival (mPFS) and median overall survival (mOS). Results We identified 17 different EGFR ex19del variants in 101 patients. Between the classic (E746_A750del, 64.4%) and nonclassic groups (the rest variants), no significant difference was observed in mPFS (13.5 vs. 19.3 months, p = 0.18) or mOS (44.1 vs. 77.0 months, p = 0.06). mPFS showed no significant difference between ex19del subgroups classified based on the presence of insertion (ex19delins), starting position or length of deletion. However, patients with ex19delins starting at E746 showed longer mPFS than the others (29.7 vs. 12.5 months, p = 0.04), and patients with ex19del of 15 nucleotides had shorter mOS than the others (44.1 vs. 77.0 months, p = 0.03). In multivariate analysis, ex19delins independently predicted a better PFS (HR = 0.311, p = 0.03); however, 15 nucleotide deletion was no longer associated with OS (HR = 0.181, p = 0.11). Secondary T790M mutation incidence was significantly higher in the ex19del subgroup starting at E746 than the others (64.7% vs. 30.8%, p = 0.04). Conclusions Our study revealed potential differences in TKI efficacy, resistance mechanism, and prognosis of various EGFR ex19del subtypes in NSCLC, underscoring the need for precise selection of first‐line therapy.