Schuetze SM, et al. - In patients with gastrointestinal stromal tumors (GISTs) treated with dasatinib, researchers evaluated the 6-month progression-free survival (PFS), tumor objective response, and overall survival rates. Findings may reveal activity of dasatinib in a subset of patients with imatinib-resistant GISTs.

Methods

• Using a Bayesian design, researchers conducted this single-arm clinical trial by enrolling patients 13 years or older with measurable imatinib-refractory metastatic GISTs treated at 14 sarcoma referral centers from June 1, 2008, through December 31, 2009. There was no control group.
• From date of enrollment, they followed up with the patients for a minimum of 5 years for survival.
• Every 8 weeks, they performed tumor imaging using computed tomography or magnetic resonance imaging for the first 24 weeks, and every 12 weeks thereafter.
• Using the Choi criteria, they assessed tumor response by local site.
• Treatment was continuous until tumor progression, unacceptable toxic effects after reduction in drug dose, or patient or physician decision.
• Archival tumor tissue was assessed for expression of the proto-oncogene tyrosine-protein kinase Src (SRC), phosphorylated SRC (pSRC), and succinate dehydrogenase complex iron sulfur subunit B (SDHB) proteins and for mutation in the V-Kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) and platelet-derived growth factor receptor α (PDGFRA) genes.
• From May 19, 2017, through December 20, 2017, they performed data analysis.
• Intervention included 70 mg orally twice daily dasatinib.
• Primary end point was the 6-month PFS estimate using greater than 30% as evidence of an active drug and less than 10% as evidence of inactive treatment.

Results

• Researchers enrolled 50 patients in this study; median age, 60 years; age range, 19-78 years; 31 (62%) male and 19 (38%) female; 41 (82%) white.
• Of these, 48 were evaluable for response.
• In the overall population, the estimated 6-month PFS rate was 29%; it was 50% in a subset of 14 patients with pSRC in GISTs.
• They observed objective tumor response in 25%, including 1 patient with an imatinib-resistant mutation in PDGFRA exon 18.