Zhang L, Wang Y S, Lin L Z, Yu Y F, Lu S
Department of Respiratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100005, China.
Department of Oncology, West China Hospital, Sichuan University, Chengdu 610044, China.
Zhonghua Zhong Liu Za Zhi. 2023 Apr 23;45(4):298-312. doi: 10.3760/cma.j.cn112152-20221226-00853.
MET gene is a proto-oncogene, which encodes MET protein with tyrosine kinase activity. After binding to its ligand, hepatocyte growth factor, MET protein can induce MET dimerization and activate downstream signaling pathways, which plays a crucial role in tumor formation and metastasis. Savolitinib, as a specific tyrosine kinase inhibitor (TKI) targeting MET, selectively inhibits the phosphorylation of MET kinase with a significant inhibitory effect on tumors with MET abnormalities. Based on its significant efficacy shown in the registration studies, savolitinib was approved for marketing in China on June 22, 2021 for the treatment of advanced non-small cell lung cancer with MET 14 exon skipping mutations. In addition, many studies have shown that MET TKIs are equally effective in patients with advanced solid tumors with MET gene amplification or MET protein overexpression, and relevant registration clinical studies are ongoing. The most common adverse reactions during treatment with savolitinib include nausea, vomiting, peripheral edema, pyrexia, and hepatotoxicity. Based on two rounds of extensive nationwide investigations to guide clinicians, the consensus is compiled to use savolitinib rationally, prevent and treat various adverse reactions scientifically, and improve the clinical benefits and quality of life of patients. This consensus was prepared under the guidance of multidisciplinary experts, especially including the whole-process participation and valuable suggestions of experts in Traditional Chinese Medicine, thus reflecting the clinical treatment concept of integrated Chinese and western medicines.
MET基因是一种原癌基因，其编码具有酪氨酸激酶活性的MET蛋白。MET蛋白与其配体肝细胞生长因子结合后，可诱导MET二聚化并激活下游信号通路，这在肿瘤形成和转移中起关键作用。赛沃替尼作为一种靶向MET的特异性酪氨酸激酶抑制剂（TKI），选择性抑制MET激酶的磷酸化，对存在MET异常的肿瘤具有显著抑制作用。基于其在注册研究中显示出的显著疗效，赛沃替尼于2021年6月22日在中国获批上市，用于治疗具有MET第14外显子跳跃突变的晚期非小细胞肺癌。此外，许多研究表明，MET TKIs在具有MET基因扩增或MET蛋白过表达的晚期实体瘤患者中同样有效，相关注册临床研究正在进行。赛沃替尼治疗期间最常见的不良反应包括恶心、呕吐、外周水肿、发热和肝毒性。基于两轮全国范围的广泛调研以指导临床医生，编写本共识以合理使用赛沃替尼，科学防治各种不良反应，提高患者的临床获益和生活质量。本共识在多学科专家的指导下编写，尤其包括中医专家的全程参与和宝贵建议，从而体现了中西医结合的临床治疗理念。
