The Impact of Acquired EGFR T790M Mutation and EGFR Circulating Cell-Free DNA on Survival in Patients with Lung Adenocarcinoma Following EGFR-TKI Therapy
Autor: | Hung Jen Chen, Chih Yen Tu, Wen-Chien Cheng, Te Chun Hsia |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Afatinib EGFR overall survival T790M OncoTargets and Therapy Metastasis 03 medical and health sciences 0302 clinical medicine Gefitinib Internal medicine medicine Pharmacology (medical) Epidermal growth factor receptor Liquid biopsy Original Research biology liquid biopsy business.industry medicine.disease circulating cell-free DNA respiratory tract diseases 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Adenocarcinoma Erlotinib business medicine.drug |
Zdroj: | OncoTargets and therapy |
ISSN: | 1178-6930 |
Popis: | Wen-Chien Cheng,1 Te-Chun Hsia,1,2 Chih-Yen Tu,1,2 Hung-Jen Chen1,2 1Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 2School of Medicine, College of Medicine, China Medical University, Taichung, TaiwanCorrespondence: Hung-Jen ChenDivision of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, No. 2, Yude Road, North District, Taichung City 40447, TaiwanEmail redman0127@gmail.comObjective: To utilize liquid biopsy to investigate the potential clinical factors influencing the incidence of the acquired epidermal growth factor receptor (EGFR) T790M mutation, and the impact of EGFR circulating cell-free DNA (CfDNA) on overall survival for patients with advanced EGFR-mutated adenocarcinoma resistant to first-line EGFR-tyrosine kinase inhibitor (TKI).Methods: A retrospective study was conducted to analyze EGFR-mutated stage IIIB-IV adenocarcinoma patients who received an EGFR-TKI (gefitinib, erlotinib, or afatinib) as first-line therapy and then underwent a liquid biopsy exam at disease progression.Results: A total of 135 patients were included, and the T790M mutation was detected in 51 patients (37.7%). The incidence of T790M mutation increased with the number of initial metastatic sites (p = 0.015). Liver metastasis (odds ratio [OR], 3.373; p = 0.017) and other metastasis (OR, 3.063; p = 0.023) were also independently correlated with T790M mutation incidence. T790M mutation was also associated with more than two progressive sites (OR, 3.382; p = 0.006), liver progression (OR, 6.204; p = 0.002), and bone progression (OR, 3.366; p = 0.004). However, central nervous system progression was inversely correlated with T790M mutation (OR, 0.183; p = 0.027). Overall survival was the longest among the patients without CfDNA, followed by those shedding T790M mutation and those shedding Del 19/L858R mutations (p = 0.005).Conclusion: Initial metastasis to the liver and other sites may be independent factors for secondary EGFR T790M mutation. T790M-positive lung adenocarcinoma has specific progression patterns. Moreover, not having EGFR CfDNA, being positive for Del19/L858R mutations, and being positive for T790M mutation have differing impacts on overall survival for patients with advanced EGFR-mutated adenocarcinoma resistant to first-line EGFR-TKI.Keywords: circulating cell-free DNA, EGFR, liquid biopsy, overall survival, T790M |
Databáze: | OpenAIRE |
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