Phase 3 study of intensive chemotherapy with or without dasatinib in core-binding factor acute myeloid leukemia Open Access

• The addition of dasatinib to chemotherapy did not improve event-free and overall survival in patients with core-binding factor AML

• The addition of dasatinib to chemotherapy was associated with increased toxicity

Background: Core-binding factor acute myeloid leukemia (CBF-AML) is associated with KIT mutations and deregulated expression of KIT.Aims: We report results from the randomized, open-label, phase 3 trial of intensive chemotherapy with or without the multi-kinase inhibitor dasatinib in adult patients with CBF-AML.Methods: Patients received "3+7" induction therapy, followed by 4 cycles of high-dose cytarabine; in the investigational arm, patients received dasatinib 100 mg QD on days 8-21 in induction, and on days 6-28 in consolidation cycles, followed by 12-month single-agent dasatinib 100 mg QD. Primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival, relapse-free survival, and cumulative incidence of relapse.Results: 202 patients were randomly assigned to the standard arm (n=102) and to the dasatinib arm (n=100). Median age was 49 years (range, 18, 77); 94 patients had t(8;21), 108 had inv(16)/t(16;16); 58 (28.7%) patients had a KIT co-mutation. There was no statistically significant difference in EFS (HR 0.92, 95%-CI 0.63, 1.33; p=0.66) or secondary endpoints between treatment arms. There was also no significant difference in EFS in subgroup analyses according to age, CBF-AML type, and KIT mutation status. The incidence of serious adverse events was higher in the investigational arm (64%) than in the standard arm (36%).Conclusion: In patients with CBF-AML, the addition of dasatinib to intensive chemotherapy failed to improve survival outcomes. The addition of dasatinib was associated with an increase in toxicity. This trial was registered at www.clinicaltrials.gov as NCT02013648.