"Activity of Anlotinib in the Second-Line Therapy of Metastatic Gastrointestinal Stromal Tumors: A Prospective, Multicenter, In Vitro Study"

作者全名："Zhou, Yongjian; Zeng, Chunling; Sun, Xiaofeng; Zhang, Jun; Qu, Hongyan; Zhang, Xinhua; Zhou, Ye; Liu, Zimin; Wu, Xiaojun; Wu, Xin; Jiao, Xuelong; Shen, Lin; Zhou, Yanbing; Wang, Yuexiang; Li, Jian"

作者地址："[Zhou, Yongjian] Fujian Med Univ, Union Hosp, Dept Gastr Surg, Fuzhou, Fujian, Peoples R China; [Zeng, Chunling; Wang, Yuexiang] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Tissue Microenvironm & Tumor, Shanghai, Peoples R China; [Sun, Xiaofeng] Nanjing Med Univ, Jiangsu Canc Hosp, Dept Internal Med, Nanjing, Jiangsu, Peoples R China; [Sun, Xiaofeng] Nanjing Med Univ, Jiangsu Inst Canc Res, Nanjing, Jiangsu, Peoples R China; [Sun, Xiaofeng] Nanjing Med Univ, Affiliated Canc Hosp, Nanjing, Jiangsu, Peoples R China; [Zhang, Jun] Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing, Peoples R China; [Qu, Hongyan] Harbin Med Univ, Canc Hosp, Gastroenterol Dept, Ward 2, Harbin, Heilongjiang, Peoples R China; [Zhang, Xinhua] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Guangzhou, Guangdong, Peoples R China; [Zhou, Ye] Fudan Univ, Shanghai Canc Ctr, Dept Gastr Surg, Shanghai, Peoples R China; [Liu, Zimin] Qingdao Univ, Affiliated Hosp, Dept Oncol, Qingdao, Shandong, Peoples R China; [Wu, Xiaojun] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Dept Colorectal Surg,State Key Lab Oncol South Pe, Ctr Canc, Guangzhou, Peoples R China; [Wu, Xin] Gen Hosp Peoples Liberat Army, Dept Gen Surg, Beijing, Peoples R China; [Jiao, Xuelong; Zhou, Yanbing] Qingdao Univ, Dept Gastrointestinal Surg, Affiliated Hosp, Qingdao, Shandong, Peoples R China; [Shen, Lin; Li, Jian] Peking Univ, Beijing Canc Hosp & Inst, Lab Carcinogenesis & Translat Res, Dept GI Oncol,Sch Oncol,Minist Educ, Beijing, Peoples R China"

通信作者："Wang, YX (通讯作者)，Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Tissue Microenvironm & Tumor, Shanghai, Peoples R China.; Zhou, YB (通讯作者)，Qingdao Univ, Dept Gastrointestinal Surg, Affiliated Hosp, Qingdao, Shandong, Peoples R China.; Li, J (通讯作者)，Peking Univ, Beijing Canc Hosp & Inst, Lab Carcinogenesis & Translat Res, Dept GI Oncol,Sch Oncol,Minist Educ, Beijing, Peoples R China."

来源：ONCOLOGIST

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000930389500001

JCR分区：Q1

影响因子：5.8

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：gastrointestinal stromal tumor; anlotinib; antitumor activity; second-line treatment

摘要："This article reports on the inhibitory effect of anlotinib in GIST cell lines with different gene mutations, evaluating the efficacy and safety of second-line treatment of GIST with anlotinib compared with second-line treatment with sunitinib in the same period. The clinical trial registration number is NCT04106024. Background Anlotinib is a multi-target tyrosine kinase inhibitor that can effectively inhibit tumor cell proliferation after receptor kinase activation caused by KIT gene mutation. Methods We tested the inhibitory effect of anlotinib in GIST cell lines with different gene mutations and evaluated the efficacy of anlotinib for patients with metastatic GIST after imatinib failure in a multicenter, single-arm, phase II study. Results In vitro, V654A mutation encoded by KIT exon 13 was intermediately sensitive to anlotinib. Moreover, anlotinib was able to partly suppress the activation loop mutation D820A from exon 17 while another activation loop mutation N822K, also from exon 17, was resistant to anlotinib. From September 2018 to October 2020, 64 patients from 9 Chinese medical centers were enrolled in this study. Seven patients had partial response and 39 patients had stable disease. The median PFS was 8.0 months. There was no statistical significance comparing with PFS of sunitinib second-line therapy at the same period. The most common adverse events related to anlotinib treatment were hypertension, neutropenia, and fatigue. Conclusion Anlotinib showed moderate antitumor activity in drug-resistant GIST cell lines in vitro, and good PFS and better tolerance in second-line therapy study."

基金机构："Chia Tai Tianqing Pharmaceutical Group Co., Ltd"

基金资助正文："Funding was provided by Chia Tai Tianqing Pharmaceutical Group Co., Ltd"