Henrique Orlandi Mourao
Micrograph showing AML Image from Paulo
The U.S. Food and Drug Administration (FDA) has accepted for priority review a new drug application (NDA) for the FLT3 inhibitor quizartinib.
With this NDA, Daiichi Sankyo is seeking approval for quizartinib to treat adults with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML).
The FDA grants priority review to applications for products that are expected to provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The FDA aims to take action on a priority review application within 6 months rather than the standard 10 months.
The FDA is expected to make a decision on the quizartinib NDA by May 25, 2019.
In addition to priority review, quizartinib has breakthrough therapy designation and fast track designation from the FDA.
Trial results
The NDA for quizartinib is supported by results from the phase 3 QuANTUM-R study. Topline results from this study were presented at the 23rd Congress of the European Hematology Association in June, and new analyses are set to be presented at the 2018 ASH Annual Meeting in December (abstract 563).
QuANTUM-R enrolled adults with FLT3-ITD AML (at least 3% FLT3-ITD allelic ratio) who had refractory disease or had relapsed within 6 months of their first complete response (CR).
Patients were randomized to receive once-daily treatment with quizartinib (n=245) or a salvage chemotherapy regimen (n=122)—low-dose cytarabine (LoDAC, n=29); combination mitoxantrone, etoposide, and cytarabine (MEC, n=40); or combination fludarabine, cytarabine, and idarubicin (FLAG-IDA, n=53).
Patients who responded to treatment could proceed to hematopoietic stem cell transplant (HSCT), and those in the quizartinib arm could resume quizartinib after HSCT.
In all, 241 patients received quizartinib, and 94 received salvage chemotherapy—LoDAC (n=22), MEC (n=25), and FLAG-IDA (n=47). Of the 28 patients in the chemotherapy group who were not treated, most withdrew consent.
Thirty-two percent of quizartinib-treated patients and 12% of the chemotherapy group went on to HSCT.
Efficacy
The median follow-up was 23.5 months. The efficacy results include all randomized patients.
The overall response rate was 69% in the quizartinib arm and 30% in the chemotherapy arm. The composite CR rate was 48% in the quizartinib arm and 27% in the chemotherapy arm. This includes:
- The CR rate (4% and 1%, respectively)
- The rate of CR with incomplete platelet recovery (4% and 0%, respectively)
- The rate of CR with incomplete hematologic recovery (40% and 26%, respectively).
The median event-free survival was 6.0 weeks in the quizartinib arm and 3.7 weeks in the chemotherapy arm (hazard ratio=0.90, P=0.1071).
The median overall survival was 6.2 months in the quizartinib arm and 4.7 months in the chemotherapy arm (hazard ratio=0.76, P=0.0177). The 1-year overall survival rate was 27% and 20%, respectively.
Safety
The safety results include only patients who received their assigned treatment.
Grade 3 or higher hematologic treatment-emergent adverse events occurring in at least 5% of patients (in the quizartinib and chemotherapy groups, respectively) included:
- Thrombocytopenia (35% and 34%)
- Anemia (30% and 29%)
- Neutropenia (32% and 25%)
- Febrile neutropenia (31% and 21%)
- Leukopenia (17% and 16%).
Grade 3 or higher non-hematologic treatment-emergent adverse events occurring in at least 5% of patients (in the quizartinib and chemotherapy groups, respectively) included:
- Sepsis/septic shock (16% and 18%)
- Hypokalemia (12% and 9%)
- Pneumonia (12% and 9%)
- Fatigue (8% and 1%)
- Dyspnea (5% for both)
- Hypophosphatemia (5% for both).