Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD–mutated, relapsed or refractory AML
| Autor: | Guy Gammon, Jean Pierre Marie, Denise Trone, Stuart L. Goldberg, Martin S. Tallman, Giovanni Martinelli, Gary J. Schiller, Mark J. Levis, Alexander E. Perl, Hagop M. Kantarjian, Jorge E. Cortes |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Myeloid 0301 basic medicine Gastrointestinal Diseases Salvage therapy Kaplan-Meier Estimate Cardiorespiratory Medicine and Haematology Biochemistry Gastroenterology chemistry.chemical_compound 0302 clinical medicine Gene Duplication Cancer Oncogene Proteins Pediatric Leukemia Hematology Middle Aged Tandem Repeat Sequences 6.1 Pharmaceuticals 030220 oncology & carcinogenesis Female Drug Adult Pediatric Research Initiative medicine.medical_specialty Heart Diseases Childhood Leukemia Pediatric Cancer Clinical Trials and Supportive Activities Clinical Sciences Immunology Antineoplastic Agents Acute QT interval Dose-Response Relationship Paediatrics and Reproductive Medicine Young Adult 03 medical and health sciences Rare Diseases Refractory Clinical Research Quizartinib Dihydrochloride Internal medicine medicine Humans Benzothiazoles Dosing Fusion Protein Kinase Inhibitors Aged Quizartinib Salvage Therapy Surrogate endpoint business.industry Phenylurea Compounds Evaluation of treatments and therapeutic interventions Cell Biology Hematologic Diseases Transplantation 030104 developmental biology fms-Like Tyrosine Kinase 3 chemistry business |
| Zdroj: | Blood, vol 132, iss 6 Cortes, JE; Tallman, MS; Schiller, GJ; Trone, D; Gammon, G; Goldberg, SL; et al.(2018). Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD-mutated, relapsed or refractory AML. BLOOD, 132(6), 598-607. doi: 10.1182/blood-2018-01-821629. UCLA: Retrieved from: http://www.escholarship.org/uc/item/1zw0t5wd |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2018-01-821629 |
| Popis: | This randomized, open-label, phase 2b study (NCT01565668) evaluated the efficacy and safety of 2 dosing regimens of quizartinib monotherapy in patients with relapsed/refractory (R/R) FLT3-internal tandem duplication (ITD)-mutated acute myeloid leukemia (AML) who previously underwent transplant or 1 second-line salvage therapy. Patients (N = 76) were randomly assigned to 30- or 60-mg/day doses (escalations to 60 or 90 mg/day, respectively, permitted for lack/loss of response) of single-agent oral quizartinib dihydrochloride. Allelic frequency of at least 10% was defined as FLT3-ITD-mutated disease. Coprimary endpoints were composite complete remission (CRc) rates and incidence of QT interval corrected by Fridericia's formula (QTcF) of more than 480 ms (grade 2 or greater). Secondary endpoints included overall survival (OS), duration of CRc, bridge to transplant, and safety. CRc rates were 47% in both groups, similar to earlier reports with higher quizartinib doses. Incidence of QTcF above 480 ms was 11% and 17%, and QTcF above 500 ms was 5% and 3% in the 30- and 60-mg groups, respectively, which is less than earlier reports with higher doses of quizartinib. Median OS (20.9 and 27.3 weeks), duration of CRc (4.2 and 9.1 weeks), and bridge to transplant rates (32% and 42%) were higher in the 60-mg groups than in the 30-mg group. Dose escalation occurred in 61% and 14% of patients in the 30- and 60-mg groups, respectively. This high clinical activity of quizartinib at the evaluated doses is consistent with previous reports with an improved safety profile. Need to dose-escalate more than half of patients who received quizartinib 30 mg also supports further investigation of treatment with quizartinib 60 mg/day. |
| Databáze: | OpenAIRE |
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