The association of acquired T790M mutation with clinical characteristics after resistance to first-line epidermal growth factor receptor tyrosine kinase inhibitor in lung adenocarcinoma
Journal
Cancer Research and Treatment
Journal Volume
50
Journal Issue
4
Pages
1294
Date Issued
2018
Author(s)
Huang, Yen-Hsiang
Hsu, Kuo-Hsuan
Tseng, Jeng-Sen
Chen, Kun-Chieh
Hsu, Chia-Hung
Chen, Jeremy J W
Yang, Tsung-Ying
Chang, Gee-Chen
Abstract
© 2018 by the Korean Cancer Association. Purpose The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients with acquired resistance after firstline EGFR-tyrosine kinase inhibitor (TKI) treatment. Materials and Methods We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFRmutation status. Results A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression- free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). Conclusion PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746- A750 mutation are associated with the frequency of T790M mutation.
Subjects
Lung neoplasms; Adenocarcinoma; Epidermal growth factor receptor mutation; T790M; Exon 19 deletion
SDGs
Other Subjects
afatinib; epidermal growth factor receptor; erlotinib; gefitinib; EGFR protein, human; epidermal growth factor receptor; protein kinase inhibitor; adult; aged; Article; cancer chemotherapy; cancer patient; cancer resistance; cancer survival; clinical evaluation; deletion mutant; exon; female; gene mutation; genetic association; human; lung adenocarcinoma; lung biopsy; major clinical study; male; metastasis; mutation rate; mutational analysis; observational study; point mutation; prevalence; progression free survival; retrospective study; survival analysis; tumor biopsy; drug resistance; genetics; lung adenocarcinoma; middle aged; pathology; point mutation; very elderly; Adenocarcinoma of Lung; Adult; Aged; Aged, 80 and over; Drug Resistance, Neoplasm; ErbB Receptors; Exons; Female; Humans; Male; Middle Aged; Mutation Rate; Point Mutation; Progression-Free Survival; Protein Kinase Inhibitors; Retrospective Studies
Publisher
KOREAN CANCER ASSOCIATION
Type
journal article