Dasatinib appears to be of benefit in certain patients with advanced gastrointestinal stromal tumors (GISTs) refractory to imatinib, according to a single-arm open-label trial. But the findings are not clear-cut.

As Dr. Scott M. Schuetze told, "One of the primary implications of our clinical trial is that further research into the role of the tyrosine kinase, SRC, in GIST as a potential biomarker for patient benefit from treatment with dasatinib or related SRC kinase inhibitor is warranted and needed."

In a paper online in JAMA Oncology, Dr. Schuetze of the University of Michigan, Ann Arbor, and colleagues report on 50 patients with imatinib-refractory GISTs. Most had also been treated with sunitinib.

Expression of SRC

They evaluated archival tumor tissue for expression of SRC, phosphorylated SRC (pSRC), succinate dehydrogenase complex iron-sulfur subunit B (SDHB) proteins and other potential biomarkers.

The patients were given dasatinib 70 mg orally twice daily for six months. Because of toxic effects, 18 patients required a temporary hold on treatment and nine required dose reduction. However, all but two completed the study.

The estimated six-month progression-free survival (PFS) rate was 29% in the overall population and 50% in a subset of 14 patients with pSRC in their GISTs. Univariate analysis also identified an association between SDH-deficient GISTs and improved PFS.

Nevertheless, median overall survival was 19 months and only 18% of patients survived more than 5 years after enrollment.

Thus, concluded Dr. Schuetze, "Additional drug discovery and clinical trials are needed to define better treatment options for patients with advanced or metastatic GIST that is resistant to imatinib and sunitinib, and for patients with SDH-deficient GIST, for whom standard drug therapy has not been established."