Dasatinib may be an effective treatment for patients with gastrointestinal stromal tumors (GISTs) resistant to imatinib, according to a study published in JAMA Oncology.1
Imatinib, a tyrosine kinase inhibitor, is a primary therapy for patients with metastatic or unresectable GISTs, but some patients present with imatinib-refractory disease. These patients’ tumors are often characterized by KIT or PDGFRA mutations. Previous studies suggested that dasatinib — a KIT, PDGFR, and SRC inhibitor — may be effective in these cases.
For this single-arm, prospective clinical trial, researchers assigned 50 patients with unresectable, recurrent, or metastatic GIST that failed imatinib therapy to receive dasatinib 70 mg twice daily. Eligible patients were 13 years or older; previous treatment with sorafenib and regorafenib was not required, though it was allowed. Patients underwent tumor imaging with computed tomography or magnetic resonance imaging within 2 weeks of enrollment, every 2 months for the first 6 months, and then every 3 months thereafter.
Of the 50 enrolled patients, 48 were evaluable. The estimated 6-month progression-free survival (PFS) rate was 29% in the entire study population. The PFS rate was, however, 50% in a subset of 14 patients who had activated Src (pSRC) — a proto-oncogene tyrosine-protein kinase thought to play a role in GIST pathogenesis.
An objective tumor response was reported in 25% of patients, including in 1 patient who had an imatinib-resistant mutation in PDGFRA exon 18.
The authors concluded that “dasatinib may have activity in a subset of patients with imatinib-resistant GISTs. Further study is needed to determine whether pSRC is a prognostic biomarker.”
- Schuetze SM, Bolejack V, Thomas DG, et al. Association of dasatinib with progression-free survival among patients with advanced gastrointestinal stromal tumors resistant to imatinib. JAMA Oncol. 2018 Apr 26. doi: 10.1001/jamaoncol.2018.0601 [Epub ahead of print]