Receptor Tyrosine Kinase Fusion-Mediated Resistance to EGFR TKI in EGFR-Mutant NSCLC: A Multi-Center Analysis and Literature Review

作者：Yang Xia, Kaiwen Wang, Jing Zhao, Zhaohui Arter, Yongchang Zhang, Jiaqi Zhou, Yuefei Lu, Liang Zeng, Robyn Du, Jennifer Owens, Yasir Y. Elamin, Carl M. Gay, Ferdinandos Skoulidis, Anne S. Tsao, Charles Lu, Tina Cascone, Don L. Gibbons, Jianjun Zhang, Olivia Chen, Kevin Mok, Misako Nagasaka, Wen Li, John V. Heymach, Sai‐Hong Ignatius Ou, Molly Li, Xiuning Le · 发表于：Journal of Thoracic Oncology · 年份：2024 · DOI：10.1016/j.jtho.2024.11.027 · 被引用次数：21 · 研究领域：Lung Cancer Treatments and Mutations、Gastrointestinal Tumor Research and Treatment、Colorectal Cancer Treatments and Studies

INTRODUCTION: Drug resistance remains a major clinical challenge in EGFR-mutant NSCLC tumors owing to pathway reactivation, pathway bypass, and pathway indifference resistance mechanisms to evade tyrosine kinase inhibitor (TKI) suppression. Fusion of receptor tyrosine kinases (RTKs), such as RET, ALK, and FGFR3, has been reported to mediate EGFR TKI resistance. Given the rarity of these fusions and the heterogeneous nature of the condition, no prospective clinical trials evaluated the incidence, safety, and therapeutic benefit of dual EGFR-RTK inhibition. METHODS: We queried clinical databases from multiple institutions to identify patients who had RTK fusions detected on next-generation sequencing testing results from tissue or blood at five institutions: the Second Affiliated Hospital Zhejiang University School of Medicine, Hunan Cancer Hospital, Prince of Wales Hospital Chinese University of Hong Kong, Chao Family Cancer Center, and the University of Texas MD Anderson Cancer Center from March 1, 2016, to September 30, 2023. The data analyzed included objective response rate (ORR) to treatment post RTK fusion detection, duration of treatment, and safety. A comprehensive literature search was conducted to identify patients with RTK fusion as the primary resistance mechanism in EGFR-mutated NSCLC patients. RESULTS: Twenty-seven patients were identified to be eligible in the analysis. ALK fusions were most reported (42.9%), followed by RET fusions (35.7%). Fifteen patients rec...