作者
Geoffrey R Oxnard, Yuebi Hu, Kathryn F Mileham, Hatim Husain, Daniel B Costa, Philip Tracy, Nora Feeney, Lynette M Sholl, Suzanne E Dahlberg, Amanda J Redig, David J Kwiatkowski, Michael S Rabin, Cloud P Paweletz, Kenneth S Thress, Pasi A Jänne
发表日期
2018/11/1
期刊
JAMA oncology
卷号
4
期号
11
页码范围
1527-1534
出版商
American Medical Association
简介
Importance
Osimertinib mesylate is used globally to treatEGFR-mutant non–small cell lung cancer (NSCLC) with tyrosine kinase inhibitor resistance mediated by theEGFRT790M mutation. Acquired resistance to osimertinib is a growing clinical challenge that is poorly understood.
Objective
To understand the molecular mechanisms of acquired resistance to osimertinib and their clinical behavior.
Design, Setting, and Participants
Patients with advanced NSCLC who received osimertinib for T790M-positive acquired resistance to prior EGFR tyrosine kinase inhibitor were identified from a multi-institutional cohort (n = 143) and a confirmatory trial cohort (NCT01802632) (n = 110). Next-generation sequencing of tumor biopsies after osimertinib resistance was performed. Genotyping of plasma cell-free DNA was studied as an orthogonal approach, including serial plasma samples when available. The study and analysis …
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