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2018-12-21T10:25:07.000Z

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

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Dec 21, 2018
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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 23rd 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  60th 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.

Expert Opinion


  1. Cortes J. et al. Efficacy and safety of single-agent quizartinib (Q), a potent and selective FLT3 inhibitor (FLT3i), in patients (pts) with FLT3-internal tandem duplication (FLT3-ITD)–mutated relapsed/refractory (R/R) acute myeloid leukemia (AML) enrolled in the global, phase 3, randomized controlled Quantum-R trial. 2018 Dec 3; Oral Abstract #563: 60th ASH Annual Meeting and Exposition, San Diego, CA.

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