Abstract | PURPOSE: PATIENTS AND METHODS:
Quizartinib was administered orally at escalating doses of 12 to 450 mg/day to 76 patients (median age, 60 years; range, 23 to 86 years; with a median of three prior therapies [range, 0 to 12 therapies]), enrolled irrespective of FLT3-ITD mutation status in a phase I, first-in-human study in relapsed or refractory AML. RESULTS: Responses occurred in 23 (30%) of 76 patients, including 10 (13%) complete remissions (CR) of any type (two CRs, three CRs with incomplete platelet recovery [CRp], five CRs with incomplete hematologic recovery [CRi]) and 13 (17%) with partial remissions (PRs). Of 17 FLT3-ITD-positive patients, nine responded (53%; one CR, one CRp, two CRis, five PRs); of 37 FLT3-ITD-negative patients, five responded (14%; two CRps, three PRs); of 22 with FLT3-ITD-indeterminate/not tested status, nine responded (41%; one CR, three CRis, five PRs). Median duration of response was 13.3 weeks; median survival was 14.0 weeks. The most common drug-related adverse events (> 10% incidence) were nausea (16%), prolonged QT interval (12%), vomiting (11%), and dysgeusia (11%); most were ≤ grade 2. The maximum-tolerated dose was 200 mg/day, and the dose-limiting toxicity was grade 3 QT prolongation. FLT3-ITD phosphorylation was completely inhibited in an in vitro plasma inhibitory assay. CONCLUSION:
Quizartinib has clinical activity in patients with relapsed/refractory AML, particularly those with FLT3-ITD, and is associated with an acceptable toxicity profile.
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Authors | Jorge E Cortes, Hagop Kantarjian, James M Foran, Darejan Ghirdaladze, Mamia Zodelava, Gautam Borthakur, Guy Gammon, Denise Trone, Robert C Armstrong, Joyce James, Mark Levis |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 31
Issue 29
Pg. 3681-7
(Oct 10 2013)
ISSN: 1527-7755 [Electronic] United States |
PMID | 24002496
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzothiazoles
- Phenylurea Compounds
- Protein Kinase Inhibitors
- quizartinib
- FLT3 protein, human
- fms-Like Tyrosine Kinase 3
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Benzothiazoles
(adverse effects, therapeutic use)
- Electrocardiography
(drug effects)
- Female
- Humans
- Leukemia, Myeloid, Acute
(drug therapy, genetics, mortality)
- Male
- Middle Aged
- Mutation
- Phenylurea Compounds
(adverse effects, therapeutic use)
- Protein Kinase Inhibitors
(therapeutic use)
- Recurrence
- Tandem Repeat Sequences
- fms-Like Tyrosine Kinase 3
(antagonists & inhibitors, genetics)
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