Quizartinib Combined with Standard Chemotherapy Significantly Improves Overall Survival in First-Line Treatment of FLT3-ITD-Positive AML

Recently, Daiichi Sankyo Company announced that the oral FLT3 inhibitor quizartinib, in combination with standard chemotherapy, met the primary endpoint in a phase 3 clinical trial for the first-line treatment of patients with FLT3-ITD mutated acute myeloid leukemia (AML). Compared to the standard treatment control, patients receiving quizartinib combined with standard induction and consolidation chemotherapy followed by continued treatment with quizartinib monotherapy showed a significant improvement in overall survival (OS). Additionally, the drug demonstrated a favorable safety profile with no new safety signals identified.

AML is one of the most common types of leukemia in adults, accounting for about one-third of all cases. As a rapidly progressing blood and bone marrow cancer, AML causes the rapid growth of abnormal white blood cells, which not only fail to function properly but also interfere with the production of normal blood cells. The 5-year survival rate for AML patients is the lowest among all types of leukemia, and the prognosis is particularly poor for patients with FLT3-ITD mutations.

FLT3 is a transmembrane receptor tyrosine kinase protein commonly expressed by hematopoietic stem cells. It promotes cell survival, growth, and differentiation through various signaling pathways, playing a crucial role in cellular development. FLT3 gene mutations are the most common genetic variation in AML patients. FLT3-ITD is the most frequent FLT3 gene mutation, occurring in approximately one-quarter of AML patients.

Quizartinib is an oral FLT3 inhibitor. It has received Breakthrough Therapy Designation and Fast Track Status from the FDA, and has been approved in Japan.

▲Quizartinib Molecular Structure (Image Source: Ed (Edgar181), Public domain, via Wikimedia Commons)

This randomized, double-blind, placebo-controlled, multicenter Phase 3 trial enrolled a total of 539 AML patients (aged 18-75) with FLT3-ITD mutations. Patients were randomly assigned in a 1:1 ratio to receive either quizartinib or placebo, in combination with anthracycline and cytarabine drugs (standard induction and consolidation chemotherapy regimens). Eligible patients subsequently continued treatment with quizartinib monotherapy or placebo for up to 36 cycles. The primary endpoint of the trial was OS, with secondary endpoints including event-free survival (EFS), complete remission (CR), safety, and pharmacokinetics.

References:

[1] Quizartinib Added to Chemotherapy Demonstrates Superior Overall Survival Compared to Chemotherapy Alone in Adult Patients with Newly Diagnosed FLT3-ITD Positive AML. Retrieved November 19, 2021, from https://www.businesswire.com/news/home/20211118006328/en/

(Original text has been abridged)

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