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- Title
Activity of Anlotinib in the Second-Line Therapy of Metastatic Gastrointestinal Stromal Tumors: A Prospective, Multicenter, In Vitro Study.
- Authors
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
- Abstract
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.
- Subjects
DRUG efficacy; RESEARCH; IN vitro studies; GENETIC mutation; CLINICAL trials; METASTASIS; FISHER exact test; STROMAL cells; GASTROINTESTINAL tumors; PROTEIN-tyrosine kinase inhibitors; CELL survival; DESCRIPTIVE statistics; RESEARCH funding; CHI-squared test; KAPLAN-Meier estimator; CELL lines; DATA analysis software; LONGITUDINAL method; PHARMACODYNAMICS; EVALUATION
- Publication
Oncologist, 2023, Vol 28, Issue 4, pe191
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1093/oncolo/oyac271