Carlos Torrado MD , Jamie Feng MD, FRCPC , Elizabeth Faour MD, FRCPC , Natasha B. Leighl MD, MMSc, FRCPC, FASCO
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引用次数: 0
摘要
MET第14外显子跳越突变已成为NSCLC新的致癌驱动因素,现有的靶向疗法包括美国食品药品管理局批准的抑制剂卡马替尼和泰泊替尼。目前已开始描述潜在的耐药机制,包括几种靶上和靶下突变。在此,我们报告了一名原发性 MET 14 号外显子跳越突变患者出现的继发性 RET 融合,该患者在服用卡马替尼后出现了初步应答,但病情有所进展。随后,该患者同时接受了一种 RET 抑制剂(赛铂替尼)和另一种 MET 靶向治疗(替泊替尼),但均未获得临床获益。此后,该患者开始接受卡博替尼(一种对RET和MET具有活性的多激酶抑制剂)治疗,并迅速获得了临床和放射学疗效。
Cabozantinib Response in a Patient With NSCLC Harboring Both MET Exon 14 Skipping Mutation and Secondary RET Fusion: A Case Report
MET exon 14 skipping mutation has emerged as a new oncogenic driver in NSCLC with available targeted therapies, including Food and Drug Administration–approved inhibitors capmatinib and tepotinib. Potential resistance mechanisms are beginning to be described and include several on-target and off-target mutations. Here, we report an emergent secondary RET fusion in a patient with a primary MET exon 14 skipping mutation that progressed on capmatinib after the initial response. Subsequently, this patient received both a RET inhibitor (selpercatinib) followed by another MET-targeted treatment (tepotinib) without clinical benefit. Thereafter, cabozantinib, a multikinase inhibitor with activity against RET and MET was started with a rapid clinical and radiologic benefit.