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Quizartinib in Relapsed or Refractory AML

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Key Points

  • Composite complete remission was observed in approximately half of patients with FLT3-ITD mutations.
  • Remission rates were 30% to 36% in FLT3-ITD–negative patients.

In a phase II trial reported in The Lancet Oncology, Cortes et al found that the next-generation FLT3 inhibitor quizartinib had good activity in patients with relapsed or refractory acute myeloid leukemia (AML), with greater activity in patients with FLT3-ITD mutations.

Study Details

The study involved patients aged 60 years or older with relapsed or refractory disease within 1 year after first-line therapy (cohort 1, n = 157) and those aged 18 years or older with relapsed or refractory disease following salvage chemotherapy or hematopoietic stem cell transplantation (cohort 2, n = 176) from 76 sites in the United States, Europe, and Canada. Patients with an FLT3-ITD allelic frequency > 10% were considered FLT3-ITD–positive. Quizartinib was given once daily as an oral solution. After observation of QT prolongation in several of the first 17 patients treated at the initial dose of 200 mg/d, doses were changed to 135 mg/d for men and 90 mg/d for women.

The coprimary endpoints were the proportion of patients achieving a composite complete remission (defined as complete remission plus complete remission with incomplete platelet recovery plus complete remission with incomplete hematologic recovery) and the proportion of patients who achieved a complete remission.

Remission Rates

Composite complete remission was observed in 63 (56%) of 112 FLT3-ITD–positive patients and 16 (36%) of 44 FLT3-ITD–negative patients in cohort 1, with complete remission observed in 3 (3%) FLT3-ITD–positive patients and 2 (5%) FLT3-ITD–negative patients. In cohort 2, composite complete remission was observed in 62 (46%) of 136 FLT3-ITD–positive patients, with complete remission in 5 (4%), and in 12 (30%) of 40 FLT3-ITD–negative patients, with complete remission in 1 (3%). 

Adverse Events

In both cohorts combined, the most common grade 3 or worse treatment-related adverse events were febrile neutropenia (23%), anemia (23%), thrombocytopenia (12%), QT prolongation (10%), neutropenia (9%), leukopenia (7%), decreased platelet count (6%), and pneumonia (5%). The most common serious adverse events were febrile neutropenia (38%), pneumonia (12%), QT prolongation (10%), sepsis (8%), and pyrexia (5%); other serious adverse events included torsades de pointes (1 patient) and hepatic failure (2 patients). Death due to adverse events considered related to treatment occurred in 18 patients (5%), including 10 (6%) in cohort 1 and 8 (5%) in cohort 2.

The investigators concluded, “Single-agent quizartinib was shown to be highly active and generally well tolerated in patients with relapsed or refractory acute myeloid leukaemia, particularly those with FLT3-ITD mutations. These findings confirm that targeting the FLT3-ITD driver mutation with a highly potent and selective FLT3 inhibitor is a promising clinical strategy to help improve clinical outcomes in patients with very few options. Phase III studies (NCT02039726; NCT02668653) will examine quizartinib at lower starting doses.”

The study was funded by Ambit Biosciences/Daiichi Sankyo.

Jorge Cortes, MD, of the Department of Leukemia, The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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