A prospective multicenter phase II study on the efficacy and safety of dasatinib in the treatment of metastatic gastrointestinal stromal tumors failed by imatinib and sunitinib and analysis of NGS in peripheral blood.

Cancer Medicine
Ye ZhouJian Li

Abstract

Dasatinib is a small molecule tyrosine kinase inhibitor with multiple targets including kit, PDGFR, and SRC. This prospective study evaluated the efficacy and safety of dasatinib as third-line treatment for gastrointestinal stromal tumors (GIST). The study enrolled adult patients (≥18 years of age) with histologically confirmed unresectable and/or metastatic GIST whose disease progressed despite imatinib and sunitinib therapy. Dasatinib (50 mg twice daily) was given orally for 1 week and escalated to 70 mg twice daily orally. The primary endpoint was to the 3-month progression-free survival (PFS) rate. Blood samples were acquired before dasatinib therapy for examination of gene mutations by next-generation sequencing (NGS). From May 2016 to June 2018, 58 patients from 9 Chinese medical centers were enrolled in this study. The 3-month PFS rate was 53.4% and the median overall survival (OS) was 14.0 months. Neither primary nor secondary gene mutations predicted the efficacy of dasatinib. Wild-type GIST patients had longer PFS (5.5 months). The most common adverse events were anemia, proteinuria, fatigue, neutropenia, and diarrhea. The concordance of KIT/PDGFRA mutation was 61.9% between tissue and peripheral blood samples and add...Continue Reading

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Citations

Mar 3, 2021·Drugs & Aging·Monika Dudzisz-ŚledźPiotr Rutkowski
Mar 20, 2021·Nature Reviews. Disease Primers·Jean-Yves BlayMargaret von Mehren
Jun 14, 2021·International Journal of Biological Macromolecules·Zili SuoHui Li

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Methods Mentioned

BETA
PCR
genotyping
biopsy

Clinical Trials Mentioned

NCT02776878

Software Mentioned

SPSS
VarDict
FreeBayes

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