It is a small moleculereceptor tyrosine kinase inhibitor. Its molecular target isFLT3, also known asCD135 which is aproto-oncogene.[6] FLT3 mutations are among the most common mutations in acute myeloid leukemia due to internal tandem duplication of FLT3, and the presence of this mutation is a marker of adverse outcome.[7]
The most common side effects of include low white blood cell counts with or without fever, reduced levels of electrolytes (potassium, magnesium or calcium) in blood, increased levels of liver or muscles enzymes, diarrhea, ulcers or redness inside the mouth (mucositis), nausea, abdominal pain, sepsis (serious infection throughout the body and organs), headache, vomiting, and upper respiratory tract infection.[8]
It was approved for medical use in Japan in October 2019,[9] in the United States in July 2023,[3] and the European Union in November 2023.[4]
Quizartinib isindicated, in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of newly diagnosedacute myeloid leukemia with FLT3 internal tandem duplication (ITD)-positive.[3][4]
Efficacy of quizartinib with chemotherapy was evaluated in QuANTUM-First (NCT02668653), a randomized, double-blind, placebo-controlled trial of 539 participants with newly diagnosed FLT3 internal tandem duplication positive acute myeloid leukemia.[3] FLT3 internal tandem duplication status was determined prospectively with a clinical trial assay and verified retrospectively with the companion diagnostic LeukoStrat CDx FLT3 Mutation Assay.[3] Participants were randomized (1:1) to receive quizartinib (n=268) or placebo (n=271) with induction and consolidation therapy and as maintenance monotherapy according to the initial assignment.[3] There was no re-randomization at the initiation of post-consolidation therapy.[3] Participants who proceeded to hematopoietic stem cell transplantation initiated maintenance therapy after hematopoietic stem cell transplantation recovery.[3]
The main efficacy outcome measure was overall survival, measured from randomization date until death by any cause.[3] The primary analysis was conducted after a minimum follow-up of 24 months after the last patient was randomized.[3] The trial demonstrated a statistically significant improvement in overall survival for the quizartinib arm [hazard ratio (HR) 0.78; 95% CI: 0.62, 0.98; 2‑sided p=0.0324].[3] The CR rate in the quizartinib arm was 55% (95% CI: 48.7, 60.9) with a median duration of 38.6 months (95% CI: 21.9, NE), and the CR rate in those receiving placebo was 55% (95% CI: 49.2, 61.4) with a median duration of 12.4 months (95% CI: 8.8, 22.7).[3]
It reported good results in 2012, from a phase II clinical trial for refractory acute myeloid leukemia - in participants who went on to have a stem cell transplant.[11][unreliable medical source?]
As of July 2023[update], it has completed seventeen clinical trials, and another eleven are active.[12]
The application for quizartinib was denied in the European Union in 2019.[13]
In September 2023, theCommittee for Medicinal Products for Human Use of theEuropean Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Vanflyta, intended for the treatment of acute myeloid leukaemia (AML) that is FLT3-ITD positive.[4] The applicant for this medicinal product is Daiichi Sankyo Europe GmbH.[4]
Quizartinib was approved for medical use in Japan in October 2019,[9] in the United States in July 2023,[3] and the European Union in November 2023.[4][5]
^abcdefg"Vanflyta EPAR".European Medicines Agency. 21 November 2023.Archived from the original on 22 November 2023. Retrieved22 November 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ab"Vanflyta Product information".Union Register of medicinal products. 7 November 2023.Archived from the original on 13 November 2023. Retrieved13 November 2023.
^Chao Q, Sprankle KG, Grotzfeld RM, Lai AG, Carter TA, Velasco AM, et al. (December 2009). "Identification of N-(5-tert-Butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea dihydrochloride (AC220), a uniquely potent, selective, and efficacious FMS-like tyrosine kinase-3 (FLT3) inhibitor".Journal of Medicinal Chemistry.52 (23):7808–7816.doi:10.1021/jm9007533.PMID19754199.
^"Vanflyta".European Medicines Agency. 6 January 2020.Archived from the original on 27 January 2023. Retrieved6 August 2023.
^World Health Organization (2011). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 66".WHO Drug Information.25 (3).hdl:10665/74683.
Clinical trial numberNCT02668653 for "Quizartinib With Standard of Care Chemotherapy and as Continuation Therapy in Patients With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia (AML) (QuANTUM-First)" atClinicalTrials.gov
This article incorporates text from this source, which is in thepublic domain.
