EHA 2018 | Quizartinib prolonged survival in patients with FLT3-ITD RR AML – data from the phase III QuANTUM-R study

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 23^rd 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
• Safety
  • 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 inhibitor (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.