Lung Cancer with MET exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges.
Lung Cancer with MET exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges.
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DOI：
10.2147/lctt.s269307
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Mitsudomi T
中科院分区：
文献类型：
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作者：
Fujino T;Suda K;Mitsudomi T
约3%的非小细胞肺癌（NSCLC）存在MET外显子14跳跃突变（MET exon 14 skipping mutation，MET exon 14）。携带MET EX 14的NSCLC患者的特征是诊断时平均年龄超过70岁，有吸烟史，多形性癌和腺鳞状细胞癌的发生率高于腺癌。也有报道称，MET p61 ex 14的NSCLC通常存在辅驱动基因改变，如EGFR扩增（6-28%）、FGFR 1改变（5-17%）、KRAS改变（~8%）、BRAF改变（~21%）或PIK 3CA突变/扩增（~14%）。2020年，两种MET-酪氨酸激酶抑制剂（TKI）capmatinib和tepotinib获批用于携带MET靶向药物14的NSCLC，开启了MET靶向治疗的新时代。这些药物在临床试验中产生了5.4 - 12.4个月的无进展生存期;然而，也有报道称，三分之一至一半的患者对MET-TKI表现出固有的耐药性。此外，MET-TKI获得性耐药的出现是不可避免的。本文综述了MET-TKIs 14阳性NSCLC的临床和分子特征、capmatinib和tepotinib的疗效和安全性、MET-TKIs的固有和获得性耐药机制以及MET-TKIs 14阳性NSCLC的近期治疗策略。
MET exon 14 skipping mutation (MET∆ex14) is present about 3% of non-small cell lung cancers (NSCLCs). NSCLC patients with MET∆ex14 are characterized by an average age of over 70 years at diagnosis, a smoking history and a higher frequency in pleomorphic carcinoma and adenosquamous cell carcinoma than in adenocarcinoma. It has also been reported that NSCLCs with MET∆ex14 often have codriver alterations such as EGFR amplification (6–28%), FGFR1 alterations (5–17%), KRAS alterations (~8%), BRAF alterations (~21%), or PIK3CA mutation/amplification (~14%). In 2020, the approval of two MET-tyrosine kinase inhibitors (TKIs), capmatinib and tepotinib, for NSCLCs carrying MET∆ex14 dawned a new era for MET-targeted therapy. These drugs yielded progression-free survival of 5.4−12.4 months in clinical trials; however, it has also been reported that one-third to half of patients show inherent resistance to MET-TKIs. In addition, the emergence of acquired resistance to MET-TKIs is inevitable. In this review, we summarize the clinical and molecular characteristics of NSCLCs with MET∆ex14, the efficacy and safety of capmatinib and tepotinib, the inherent and acquired resistance mechanisms to MET-TKIs, and new treatment strategies for NSCLCs with MET∆ex14 in the near future.