A Case Report of Successful Treatment With Crizotinib to Overcome Resistance to Osimertinib in an EGFR Mutated Non-Small-Cell Lung Cancer Patient Harboring an Acquired MET Exon 14 Mutation
A Case Report of Successful Treatment With Crizotinib to Overcome Resistance to Osimertinib in an EGFR Mutated Non-Small-Cell Lung Cancer Patient Harboring an Acquired MET Exon 14 Mutation
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DOI：
10.1016/j.cllc.2021.06.002
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发表时间：
2022-02-25
影响因子：
3.6
通讯作者：
Molinier, Olivier
中科院分区：
文献类型：
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作者：
Pinquie, Francois;Cortot, Alexis B.;Molinier, Olivier
这个课题已知多少？在T790M阳性的非小细胞肺癌患者中，对奥西美替尼的耐药机制是多样的和异质性的，包括从头开始的EGFR改变(C797S突变)，EGFR非依赖性机制(MET和HER-2扩增)或组织学改变。METEX 14跳跃改变是一种极其罕见的对奥西美替尼的耐药机制，可以通过对现有少数亚克隆的药物选择或出现新的分子改变来解释。在少数对奥西美替尼耐药并进行了MET改变测试的患者中，在联合应用EGFRTKI和Crizotinib后，客观反应被报道。在出现Osimertinib耐药后，液体和肿瘤活检在常规治疗中很少进行。新的发现是什么，它们在可预见的未来如何影响临床实践？我们提供第一个病例报告，证明在这种情况下单独使用Crizotinib可以是有效的长期治疗。重复系列液体活检，包括胸水，甚至在终末期疾病，可能导致意外的和有针对性的分子发现，包括cfDNA的MET改变。临床肺癌，(C)2021年，爱思唯尔公司出版。
What is already known about this subject?Resistance mechanisms to osimertinib in T790M positive NSCLC patients are multiple and heterogeneous, combining de novo EGFR alterations (C797S mutation), EGFR-independent mechanisms (MET and HER-2 amplifications) or histological transformations.METex14 skipping alteration is an extremely rare resistance mechanism to osimertinib and can be explained either by drug selection of pre-existing minority subclones or by emergence of de novo molecular alteration.In the rare patients who were resistant to osimertinib and who were tested for MET alteration, objective responses were reported after a combination of EGFRTKI and crizotinib.Liquid and tumor biopsies are rarely performed in routine practice after emergence of osimertinib resistanceWhat are the new findings and how might they impact on clinical practice in the foreseeable future?We present the first case report demonstrating that crizotinib administrated alone can be effective long-term in this setting.Repeating serial liquid biopsy, including pleural fluid, even in end-stage disease, may lead to detection of unexpected and targetable molecular findings, including MET alterations in cfDNA. Clinical Lung Cancer, (C) 2021 Published by Elsevier Inc.