Quizartinib, an oral, highly potent and selective FLT3 inhibitor, led to a significant reduction in the risk of death by 24% compared to salvage chemotherapy (SC) in patients with FLT3-internal tandem duplication (FLT3-ITD) positive relapsed/refractory (R/R) acute myeloid leukemia (AML) after first-line treatment with or without hematopoietic stem cell transplantation (HSCT), according to results from the phase III randomized study (NCT02039726) presented at the 23rd Congress of the European Hematology Association, Stockholm, Sweden by Jorge Cortes from The University Texas MD Anderson Cancer Center.
The phase III QuANTUM-R study is assessing the efficacy and safety of quizartinib (60-mg, with a 30-mg lead-in for 15 days) versus SC in patients with R/R FLT3-ITD-mut AML. Overall, a total of 367 FLT3-ITD AML patients who had refractory or relapsed disease within 6 months of first remission after standard chemotherapy, were enrolled in this study. Patients were randomized 2:1 to receive quizartinib (n = 245, median age = 55 years [range; 19–81]) or investigator’s choice SC (n = 122, median age = 58 [range; 18–78]). SC choices were low dose cytarabine (LoDAC, n = 29), mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC, n = 40), or fludarabine, cytarabine, and granulocyte-colony stimulating factor with idarubicin (FLAG-IDA, n = 53).
The primary and secondary endpoints of the study were overall survival (OS) and event-free survival (EFS) respectively in the intention-to-treat (ITT) population.
Key findings at data cut-off in February 2018:
- Median follow-up: 23.5 months
- Median OS in the quizartinib and SC arms: 6.2 (95% CI, 5.2–7.2) vs 4.7 (95% CI, 4.0–5.5) months respectively, HR = 0.76, P = 0.0177
- Median EFS in the quizartinib and SC arm: 6.0 vs 3.7 weeks respectively, HR = 0.90, P = 0.1071
- Composite complete remission rate in the quizartinib and SC arms were 48% and 27% respectively
- Transplant rate in the quizartinib and SC arms were 32% and 12% respectively
- Most common all grade treatment-emergent adverse events occurring in ≥ 20% in patients treated with quizartinib vs SC, respectively, included thrombocytopenia (39% vs 34%), anemia (37% vs 32%), neutropenia (34% vs 26%), febrile neutropenia (34% vs 28%), and leukopenia (20% vs 17%)
- Two patients discontinued quizartinib treatment due to QTcF prolongation
In summary, the QuANTUM-R trial is the first study to demonstrate that a FLT3 inhibitior (quizartinib) significantly prolongs OS in R/R FLT3-ITD AML patients compared to SC. Jorge Cortes, in an interview, highlighted that the QuANTUM-R trial was a “very positive study”, which they hope would lead to a “regulatory approval” for quizartinib as it “offers an advantage” over the current treatment options for these difficult to treat patients.