Quizartinib is a small, potent, next-generation FMS-like tyrosine kinase 3 (FLT3) inhibitor in relapsed or refractory acute myeloid leukemia (R/R AML). In a May issue of Lancet Oncology, Jorge Cortes from The University of Texas MD Anderson Cancer Center, Houston, TX, USA, and colleagues published the results of an open-label, multicenter, single-arm, phase II study (NCT00989261) evaluating quizartinib in patients with morphologically documented primary AML or secondary AML.
In total, 333 patients were enrolled between November 2009 and October 2011. Patients were divided into two groups as follows: cohort 1 included 157 patients (age = 60 years or older) with relapsed/refractory (R/R) AML within one year after first-line therapy; cohort 2 included 176 patients (age = 18 years or older) with R/R AML following salvage chemotherapy or hematopoietic stem cell transplantation (HSCT). Quizartinib was administered once daily as an oral solution in 28-day treatment cycles. Patients received quizartinib until relapse, intolerance, or HSCT.
- Complete remission rates in cohort 1:
- Composite complete remission: 63/112 (56%) FLT3-ITD-positive patients and 16/44 (36%) FLT3-ITD-negative patients
- Complete remission: 3/112 (3%) FLT3-ITD-positive patients and 2/44 (5%) FLT3-ITD-negative patients
- Complete remission rates in cohort 2:
- Composite complete remission: 62/136 (46%) FLT3-ITD-positive patients and 12/40 (30%) FLT3-ITD-negative patients
- Complete remission: 5/136 (4%) FLT3-ITD-positive patients and 1/40 FLT3-ITD-negative patient
- ≥ Grade 3 treatment-related treatment-emergent adverse events included febrile neutropenia (23%), anemia (23%), thrombocytopenia (12%), QT interval corrected using QTcF prolongation (10%), neutropenia (9%), leukopenia (7%), decreased platelet count (6%), and pneumonia (5%)
- Serious adverse events included febrile neutropenia (38%), AML progression (22%), pneumonia (12%), QTcF prolongation (10%), sepsis (8%), and pyrexia (5%)
The authors concluded that single-agent quizartinib is safe and efficient in patients with R/R AML, predominantly with FLT3-ITD mutations. The study group added that “these findings confirm that targeting the FLT3-ITD driver mutation with a highly potent and selective FLT3 inhibitor is a promising clinical strategy to help improve clinical outcomes in patients with very few options. Phase 3 studies (NCT02039726; NCT02668653) will examine quizartinib at lower starting doses.”
1. Cortes J. et al. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2018 May 30. DOI: 10.1016/S1470-2045(18)30240-7