治疗NTRK融合阳性成人和儿童实体瘤患者新药larotrectinib  

A new drug for solid tumors harbouring NTRK fusions in adults and children: larotrectinib

作　　者：陈素华 张艳华[1] CHEN Su-hua;ZHANG Yan-hua(Department of Pharmacy,Cancer Hospital of Peking University and Beijing Institute of Cancer Control,Key Laboratory of Pathogenesis and Transformation of Malignant Tumor,Ministry of Education,Beijing 100142,China;Department of Clinical Pharmacy and Pharmacy Administration,School of Pharmacy,Peking University Health Science Center,Beijing 100191,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所药剂科,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142 [2]北京大学医学部药学院临床药学与药事管理系,北京100191

出　　处：《中国新药杂志》2020年第6期609-613,共5页Chinese Journal of New Drugs

摘　　要：larotrectinib是由LOXO Oncology公司和Bayer公司开发的一种新型口服高选择性的原肌球蛋白受体激酶(tropomyosin receptor kinases,TRK)抑制剂,通过可逆性与TRK结合,抑制神经营养因子受体激酶(neurotrophic receptor tyrosine kinase,NTRK)基因融合驱动的TRK非配体依赖性组成型激活的实体瘤生长。在临床试验中,larotrectinib在NTRK融合阳性,无已知获得性耐药突变的成人及儿童实体瘤患者中表现较高的总缓解率(overall response rate,ORR),且尚未发现心血管方面的安全隐患。FDA已于2018年11月26日批准larotrectinib在美国上市,是FDA批准的首个通过"篮子试验"的口服小分子靶向抗肿瘤药物。本文对larotrectinib的作用机制、药动学、临床研究、安全性、药物相互作用等进行综述。Larotrectinib is a novel oral high-selectivity tropomyosin receptor kinases(TRK) inhibitor developed by LOXO Oncology and Bayer. It inhibits the growth of solid tumors with neurotrophic receptor tyrosine kinase(NTRK) fusion which drives TRK non-ligand-dependent constitutive activation. In clinical trials, larotrectinib showed a high overall response rate(ORR) in NTRK fusion-positive solid tumors without known acquired resistance mutations in adults and children, and no cardiovascular risks were observed. The FDA approved larotrectinib on November 26, 2018. Larotrectinib is the first oral small molecule targeted antineoplastic drug passing through the "basket trials". This article summarized the basic information, mechanism of action, pharmacokinetics, clinical trials, safety, drug-drug interactions, usage and dosage, and acquired resistance mechanisms of larotrectinib.

关 键 词：larotrectinib TRK抑制剂 NTRK融合 临床研究 获得性耐药 

分 类 号：R979.1[医药卫生—药品]