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.
Keywords: anlotinib; antitumor activity; gastrointestinal stromal tumor; second-line treatment.
© The Author(s) 2023. Published by Oxford University Press.