Mesenchymal-epithelial transition factor (MET) gene mutation is a large class of mutations commonly seen in non-small cell lung cancer (NSCLC). MET mutation includes subtypes such as MET exon 14 skipping mutation (METex14m) and MET amplification (METamp). For advanced NSCLC with METex14m, Savolitinib has a high sensitivity as a member of tyrosine kinase inhibitors (TKIs). METamp is a relatively rare genetic mutation type which can serve as a driver gene to mediate primary and later acquired drug resistance of epidermal growth factor receptor (EGFR)-TKIs. For advanced NSCLC with secondary METamp, EGFR-TKIs combined with MET-TKIs are usually used in clinical treatment, while the optimal treatment strategy for advanced NSCLC with primary METamp has not yet been determined. For locally advanced NSCLC patients with positive driver gene mutations such as EGFR, anaplastic lymphoma kinase (ALK) fusion and METex14m, there have been relevant cases reported that neoadjuvant targeted therapy could achieve a good prognosis, but there have been no cases of neoadjuvant targeted therapy for locally advanced NSCLC patients with METamp. This report describes a case of a locally advanced NSCLC patient with dual driver gene mutations (EGFR L858R combined with primary METamp), the tumor did not shrink after 1 month of Gefitinib monotherapy, but significantly subsided after 4 months of Savolitinib monotherapy. After radical surgery, the pathological results proved pathological complete response (pCR) of the tumor, and the patient had a good response to postoperative continual Savolitinib treatment, with no recurrence nor metastasis observed to date. This case reports the feasibility and effectiveness of neoadjuvant targeted therapy for locally advanced NSCLC with primary METamp, aiming to provide effective reference for perioperative treatment of locally advanced NSCLC with primary METamp. .
【中文题目：赛沃替尼诱导MET扩增非小细胞肺癌 病理学完全缓解1例】 【中文摘要：间质-上皮细胞转化因子（mesenchymal-epithelial transition factor, MET）基因突变是非小细胞肺癌（non-small cell lung cancer, NSCLC）中常见的一类基因突变，包括MET外显子14跳跃突变（MET exon 14 skipping mutation, METex14m）和MET扩增（MET amplification, METamp）等类型。针对具有METex14m的晚期NSCLC，赛沃替尼（Savolitinib）这种酪氨酸激酶抑制剂（tyrosine kinase inhibitors, TKIs）具有较高的敏感性。METamp是一种较为罕见的NSCLC中的基因突变类型，可以作为驱动基因介导表皮生长因子受体（epidermal growth factor receptor, EGFR）-TKIs的原发性耐药和后期药物获得性耐药。对于EGFR-TKIs诱导产生的继发性METamp突变晚期NSCLC，临床多采取在EGFR-TKIs基础上联合MET-TKIs进行治疗，而针对原发性METamp突变晚期NSCLC的最佳治疗策略尚未确定。对于EGFR、间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）融合、METex14m等驱动基因突变阳性的局部晚期NSCLC患者，通过新辅助靶向治疗获得良好预后已有相关病例报道，但目前尚未有METamp突变的局部晚期NSCLC患者进行新辅助靶向治疗的案例。本文报道了1例存在双驱动基因突变（EGFR L858R合并原发METamp）的局部晚期NSCLC患者，经过吉非替尼单药治疗1个月后肿瘤未见缩小，更换为赛沃替尼单药治疗4个月诱导后肿瘤明显消退，根治性手术切除后病理结果提示肿瘤获得病理学完全缓解，术后患者对持续赛沃替尼治疗反应良好，至今未见肿瘤复发或转移。本文首次报道了原发METamp突变的局部晚期NSCLC患者行新辅助靶向治疗的可行性和有效性，以期为原发METamp突变局部晚期NSCLC的围手术期治疗提供有效借鉴。 】 【中文关键词：肺肿瘤；新辅助靶向治疗；MET扩增；赛沃替尼；病理学完全缓解】.
Keywords: Lung neoplasms; MET amplification; Neoadjuvant targeted therapy; Pathological complete response; Savolitinib.