An Observational Study of AcquiredEGFRT790M-Dependent Resistance to EGFR-TKI Treatment in Lung Adenocarcinoma Patients in Taiwan

doi:10.3389/fonc.2020.01481

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24920

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24920

Title:	An Observational Study of AcquiredEGFRT790M-Dependent Resistance to EGFR-TKI Treatment in Lung Adenocarcinoma Patients in Taiwan
Authors:	Wu, SG;Chiang, CL;Liu, CY;Wang, CC;Su, PL;Hsia, TC;Shih, JY;Chang, GC
Keywords:	afatinib;epidermal growth factor receptor mutation;erlotinib;gefitinib;non-small cell lung cancer;tyrosine kinase inhibitor;osimertinib
Date:	2020
Issue Date:	2022-08-09T08:10:10Z (UTC)
Publisher:	FRONTIERS MEDIA SA
ISSN:	2234-943X
Abstract:	In Taiwan, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs), gefitinib, erlotinib, and afatinib are served as first-line therapy for non-small lung cell cancer (NSCLC) patients withEGFRsensitizing mutations. However, the majority of patients who initially respond to EGFR-TKIs, progress through acquiringEGFRT790M mutations (T790M), which is the most common resistant mechanism. Patients with T790M gain the opportunity of subsequent treatment with third-generation EGFR-TKI, osimertinib. This study aimed to evaluate the association between prior EGFR-TKI therapy and incidence of acquired T790M resistance in lung adenocarcinoma patients who have progressed on first/second-generation EGFR-TKI therapy. This retrospective study included lung adenocarcinoma patients who had a radiographically-confirmed progressive disease under EGFR-TKI treatment and had re-biopsy samples for T790M testing from seven medical centers in Taiwan from June 2013 to December 2018. Patients harboringde novoT790M or using more than one EGFR-TKI were excluded. Of the 407 patients enrolled, the overall T790M acquisition rate was 52.8%. The patients treated with gefitinib, erlotinib or afatinib had a statistically significant difference in the T790M rates (59.9, 45.5, and 52.7%, respectively;p= 0.037) after disease progression. Patients with common baselineEGFRmutations (Del-19 and L858R) (p= 0.005) and longer treatment duration with EGFR-TKIs (p< 0.001) had higher chances of T790M acquisition. Multivariate logistic regression analysis further showed that patients with common baselineEGFRmutations, gefitinib (compared to erlotinib) administration, and longer treatment duration with EGFR-TKIs had higher T790M incidence. There was no significant difference in the incidence of acquired T790M between different re-biopsy tissue samples or complications. In conclusion, this study showed that patients who progressed from gefitinib treatment, bearing commonEGFRmutations, and with longer EGFR-TKI treatment duration had increased incidence of T790M acquisition and, therefore, were suitable for subsequent osimertinib treatment.
URI:	http://dx.doi.org/10.3389/fonc.2020.01481 https://www.webofscience.com/wos/woscc/full-record/WOS:000572261400001 https://ir.csmu.edu.tw:8080/handle/310902500/24920
Relation:	FRONTIERS IN ONCOLOGY ,2020 ,v10
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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