Dasatinib/Startase misses core binding factor AML survival endpoint

According toresults from a phase 3 trial (NCT02013648) announced at the 2025 conference, the combination with core binding factoracute myeloid leukemia(CBF-AM L) The addition of Dasatinib to induction and consolidation therapy, followed by 12 months of maintenance therapy, did not improve event-free survival (EFS) or overall survival (OS) compared with patients' standard treatment.

In the standard-therapy group (n=102), patients' 4-year EFS rate was 41%, compared with 44% in the dasatinib group (n=100; HR, 0.92; 95% CI, 0.63-1.33; P=0.66). The 4-year OS rates in each group were 76% and 78%, respectively (HR, 0.93; 95% CI, 0.53-1.63; P=0.79). In the standard arm, the complete response (CR) rate was 64.7% and the CR rate for hematologically incomplete recovery (CRi) was 31.4%, with 1.0% of patients having refractory disease; 30-day mortality was 2%. The CR in the dasatinib arm was 55%, CRi was 36%, 1.0% of patients had refractory disease, and 30-day mortality was 3%.

Concerning allogeneic hematopoietic cell transplantation (HCT), the CR/CRi rate was 2.9% in the standard group and 3.0% in the dasatinib group. 27.5% and 29.0% of patients developed any HCT during the disease course.

For CBF-AML patients, adding dasatinib to induction and consolidation chemotherapy followed by 12 months of maintenance therapy with dasatinib did not improve EFS and OS. These data do not support the encouraging data reported in the single-arm phase 2 study and once again emphasize the importance of studying new drugs in controlled randomized trials.

A total of 204 patients were recruited between August 2014 and February 2021. Patients were randomized 1:1 to receive daunorubicin and cytarabine as induction therapy followed by four cycles of high-dose cytarabine as consolidation therapy, or to receive dasatinib 100 mg on days 8 to 21 plus daunorubicin and cytarabine for induction, followed by high-dose cytarabine and dasatinib 100 mg as consolidation therapy on days 6 to 28. In the experimental group, 100 mg of dasatinib maintenance therapy was given from days 1 to 28. Additionally, in the dasatinib group, minimal residual disease was assessed by reverse transcription quantitative polymerase chain reaction during consolidation and maintenance.

In the standard group, the median age was49.8 years old, 50% are female, AML types include de novo (93.1%), secondary (1.0%) or treatment-related (4.9%). KIT was evaluated and mutations (31.4%) included exon 8 (11.8%), exon 17 (23.5%), and exons 9 and 17 (3.9%) compared to 68.6% in wild type. FLT3 internal tandem duplication (ITD) was positive in 3.9% of patients and negative in 96.1% of patients. The positive rate of FLT3 tyrosine kinase domain (TKD) mutation was 9.8%, and the negative rate was 90.2%.

The median age in the dasatinib group was 49.7 years old, 56% of patients were female, and the AML types included de novo (84%), secondary (3%) or treatment-related (12%). KIT was evaluated, including mutated (26%), exon 8 mutated (10%), exon 17 mutated (16%), and wild-type (74%) genes. Patients were FLT3-ITD positive (1.0%) or negative (99%). Patients were FLT3-TKD positive (11%) or negative (89%).

Hematological adverse reactions (AEs) between the standard group and the dasatinib group included thrombocytopenia, leukopenia, neutropenia and anemia, respectively. Nonhematologic adverse events in the standard and dasatinib arms included febrile neutropenia, atrial fibrillation, colitis, infection, pneumonia, and pyrexia.

In the dasatinib group, 64% of patients had serious adverse events, compared with 36% in the standard group. In the dasatinib group, 41% were treatment-related. The most common serious adverse events included pneumonia/pneumonia, sepsis, febrile neutropenia, and pyrexia.

Reference materials:https://www.cancernetwork.com/view/dasatinib-misses-survival-end-points-in-core-binding-factor-aml