ASH 2018 | Final safety and efficacy data from the phase III QuANTUM-R study

The phase III QuANTUM-R randomized study (NCT02039726) is assessing the efficacy and safety of quizartinib (60 mg, with a 30 mg lead-in for 15 days), an oral, highly potent and selective FLT3 inhibitor, versus salvage chemotherapy (SC) in patients with relapsed or refractory (R/R) fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)-mutated acute myeloid leukemia (AML). Initial data presented from this study at the 23^rd Congress of the European Hematology Association (EHA), Stockholm, Sweden, by Jorge Cortes from The University Texas MD Anderson Cancer Center demonstrated that quizartinib led to a significant reduction in the risk of death by 24% compared to SC in patients with FLT3-ITD-positive R/R AML after first-line treatment with or without hematopoietic stem cell transplantation (HSCT).  The final safety and efficacy data from this study were presented by Jorge Cortes at the  60^th American Society of Hematology Annual Meeting & Exposition.

Overall, 367 FLT3-ITD AML patients who had R/R 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 were overall survival (OS) and event-free survival (EFS) in the intention-to-treat (ITT) population. The data cut-off for this study was February 2018.

Key findings

• Median follow-up: 23.5 months
  • Median OS in patients in the quizartinib and SC arms, respectively: 6.2 (95% CI, 5.3–7.2) vs 4.7 (95% CI, 4.0–5.5) months, HR = 0.76 (95% CI, 0.58–0.98), P = 0.0177
• Median EFS in patients in the quizartinib and SC arms, respectively: 1.4 (95% CI, 0.0–1.9) vs 0.9 (95% CI, 0.4–1.3) months, HR = 0.90 (95% CI, 0.70–1.16), P = 0.1071
• Composite complete response (CRc) rate in the quizartinib and SC arms: 48% (118/245) vs 27% (27/122)
  • Median duration of CRc in the quizartinib and SC arms: 4.9 (3.7–19.7) vs 0 (2.0–14.9)
• Transplant rate in patients in the quizartinib and SC arms, respectively: 32% (78/245) vs 12% (12/122), P < 0.0001
• 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%)
  • Electrocardiogram QT prolongation occurred in 27% (64/241) and 2% (2/94) of patients in the quizartinib and SC arms, respectively
    • Two patients discontinued quizartinib due to QT prolongation

In summary, the final safety and efficacy data from the phase III QuANTUM-R trial demonstrate that quizartinib was well tolerated and significantly prolongs OS in R/R FLT3-ITD AML patients compared to SC. The OS benefit for quizartinib was seen across subgroups and was reproduced consistently across sensitivity analyses.