The FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.
The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy — cytarabine and anthracycline induction followed by cytarabine consolidation — and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.
The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD [internal tandem duplication] mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation.
Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months vs 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).
Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.
In a company press release, the drug's manufacturer Daiichi Sankyo said quizartinib will be available in the US soon.
Company executive Ken Takeshita, MD, called the approval "an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive."
The FDA's original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib's Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.
Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it's only available through a new program, dubbed "Vanflyta REMS."
In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.
The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs 41% with placebo); neutropenia (18% vs 9%); hypokalemia (19% vs 16%); and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib vs 9.7% of patients on placebo, mostly due to infections.
The FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults in 2019 after most of its oncology advisors thought the risk of treatment outweighed the benefits in an earlier trial.
Lead image: Daiichi Sankyo, Inc.
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Cite this: FDA Approves Quizartinib for NewlyDiagnosed AML - Medscape - Jul 20, 2023.