特泊替尼在非小细胞肺癌中的研究进展  

Research progress of tepotinib in non-small cell lung cancer

作　　者：沈继伟 吴霜 杨睿 王欣[1] 张欣雨 多美颖 刘举[1,2] SHEN Ji-wei;WU Shuang;YANG Rui;WANG Xin;ZHANG Xin-yu;DUO Mei-ying;LIU Ju(School of Pharmacy,Liaoning University,Shenyang 110036,Liaoning Province,China;Liaoning Provincial Engineering Research Center for Small Molecule Targeted Drug,Shenyang 110036,Liaoning Province,China)

机构地区：[1]辽宁大学药学院,辽宁沈阳110036 [2]辽宁省小分子靶向药物研发工程研究中心,辽宁沈阳110036

出　　处：《中国临床药理学杂志》2025年第4期576-580,共5页The Chinese Journal of Clinical Pharmacology

基　　金：沈阳市自然科学基金资助项目(23-503-6-12)。

摘　　要：在非小细胞肺癌(NSCLC)中,经常出现的一种致癌机制是针对间质-上皮细胞转型因子(MET)基因的第14个外显子发生跳跃式突变,此变异普遍存在于NSCLC案例中,并且加快了癌症的发展。临床研究显示,特泊替尼作为首个针对MET的口服酪氨酸激酶抑制药,在晚期NSCLC中展现出显著疗效,总体缓解率(ORR)为44.7%,中位无进展生存期(PFS)为8.9~12.2个月。尽管耐药性在治疗后6~12个月内出现,但通过联合赖性表皮生长因子受体(EGFR)-酪氨酸激酶抑制药(TKIs)治疗能够克服部分由EGFR突变和MET扩增引起的耐药性。此外,特泊替尼在不同患者群体中的安全性良好,常见药物不良反应包括外周水肿、恶心和腹泻。特泊替尼可,显著延长患者的PFS。此外,其他新型MET-TKI,如卡马替尼和赛沃替尼在MET突变的NSCLC治疗中也表现出良好疗效。本文总结了特泊替尼的药理作用、耐药机制、药物不良反应及其在NSCLC中的临床应用进展。A common carcinogenic mechanism in non-small cell lung cancer(NSCLC) is a jump mutation in exon 14 of the mesenchymal epithelial transition factor(MET) gene, which is commonly present in NSCLC cases and accelerates cancer progression. Clinical studies have shown that tepotinib, as the first oral tyrosine kinase inhibitor targeting MET, exhibits significant efficacy in advanced NSCLC, with an overall response rate(ORR) of 44.7% and a median progression free survival(PFS) of 8.9 to 12.2 months. Although drug resistance appears within 6 to 12 months after treatment, combined treatment with epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs) can overcome some of the resistance caused by EGFR mutations and MET expansion. In addition, tepotinib has good safety in different patient populations, with common adverse reactions including peripheral edema, nausea, and diarrhea. Tepotinib significantly prolongs the PFS of patients. In addition, other novel MET-TKI such as carbamatinib and sevotinib have also shown good efficacy in the treatment of MET mutant NSCLC. This article summarizes the pharmacological effects, resistance mechanisms, adverse reactions, and clinical application progress of terbotinib in NSCLC.

关 键 词：特泊替尼 间质-上皮细胞转型因子激酶抑制药 药理作用 合成路线 临床评价 药物不良反应 

分 类 号：R979.1[医药卫生—药品]