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- Title
The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma.
- Authors
Yen-Hsiang Huang; Kuo-Hsuan Hsu; Jeng-Sen Tseng; Kun-Chieh Chen; Chia-Hung Hsu; Kang-Yi Su; Chen, Jeremy J. W.; Huei-Wen Chen; Sung-Liang Yu; Tsung-Ying Yang; Gee-Chen Chang
- Abstract
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
EPIDERMAL growth factor receptors; PROTEIN-tyrosine kinases; ADENOCARCINOMA; GENETIC mutation; DISEASE prevalence
- Publication
Cancer Research & Treatment, 2018, Vol 50, Issue 4, p1294
- ISSN
1598-2998
- Publication type
Article
- DOI
10.4143/crt.2017.512