Anlotinib has moderate antitumor activity in drug-resistant gastrointestinal stromal tumor (GIST) cells grown in culture, showed a new study published in The Oncologist. It also leads to progression-free survival and is better tolerated as second-line therapy in patients with GIST.
“This is the first clinical study to evaluate the treatment of GIST with anlotinib,” the researchers wrote.
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“Although no randomized control was conducted, data from patients treated during the same time period were used for comparison, and the results are encouraging. This research data is of positive significance for further research on anlotinib,” they added.
To test the potential role of anlotinib in GIST, a team of researchers from China tested the inhibitory effect of the treatment in cell lines harboring different mutations. They also tested its efficacy in a phase 2 clinical trial in 64 patients with metastatic GIST whose disease did not respond to imatinib treatment.
The results showed that in cell culture, the V654A mutation encoded by KIT exon 13 was intermediately sensitive to anlotinib treatment. Anlotinib was also able to partly suppress the activation loop mutation D820A from exon 17. However, another activation loop mutation N822K from exon 17, was not responsive to anlotinib treatment.
In the clinical trial, 7 patients partially responded to anlotinib treatment, while 29 had stable disease following treatment. The median progression-free survival was 8 months.
The most common adverse events associated with the use of anlotinib were high blood pressure, neutropenia, and fatigue.
Anlotinib is a multireceptor tyrosine kinase inhibitor that targets vascular endothelial growth receptor type 2 and type 3, among others, inhibiting angiogenesis and halting the growth of tumor cells.
GIST is a rare type of soft-tissue tumor that develops from the interstitial cells of Cajal, which are located in the wall of the gastrointestinal tract.
Reference
Zhou Y, Zeng C, Sun X, et al. Activity of anlotinib in the second-line therapy of metastatic gastrointestinal stromal tumors: A prospective, multicenter, in vitro study. Oncologist. Published online February 13, 2023. doi:10.1093/oncolo/oyac271
Efficacy and safety of anlotinib in patients with advanced gastrointestinal stromal tumor after failure of imatinib: a prospective, single-arm and multicenter trial. US National Library of Medicine. Updated September 26, 2019. Accessed February 15, 2023.
