The FDA has prioritised reviewing quizartinib, a selective inhibitor of FLT-3, for a subgroup of patients with acute myeloid leukaemia (AML). The priority has been awarded based on the findings of the QuANTUM-First trial.
FMS-like tyrosine kinase 3 (FLT3)- internal tandem duplication (ITD) is a common driver mutation in approximately 25% of AML cases. It is associated with unfavourable clinical outcomes and shorter overall survival (OS). Daiichi Sankyo has developed a selective oral inhibitor of FLT-3, quizartinib, whose efficacy has been evaluated in the phase III QuANTUM-First trial.
The randomized phase III QuANTUM-First trial enrolled 539 AML patients (median age 56 years) with FLT3-ITD mutations. The participants were randomized (1:1) to either receive quizartinib (n=268) or placebo (n=271) in combination with standard induction (cytarabine and anthracycline) and consolidation chemotherapy (cytarabine). The study’s primary endpoint was OS, whereas the secondary endpoints included event-free survival (EFS), complete remission (CR), composite CR, and safety.
After a median follow-up of 39.2 months, the OS was improved in the quizartinib arm as compared to the placebo (median 31.9 months vs 15.1 months; HR [95% CI]: 0.77 [0.61-0.97]). The safety profile of quizartinib was found to be manageable.
There is an unmet need for treating AML patients with FLT-3 mutations. Therefore, the FDA’s priority for quizartinib reflects the promising results of the QuANTUM-First trial and the potential the drug combination has for changing clinical outcomes in AML.