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AACR 2019: Gilteritinib in patients with FLT3-mutated acute myeloid leukemia


Patients assigned to Gilteritinib ( Xospata ) were found to have a 36% reduction in risk of death compared with those assigned to standard chemotherapy.
Median overall survival was 9.3 months for those assigned to Gilteritinib vs 5.6 months for those assigned to standard chemotherapy.
The 1-year survival rate was 37.1% in the Gilteritinib-treated group compared with 16.7% among those receiving standard chemotherapy.
Treatment with the FLT3-targeted therapeutic Gilteritinib has improved survival for patients with relapsed or refractory acute myeloid leukemia ( AML ) harboring an FLT3 mutation compared with standard chemotherapy regimens, according to results from the phase III ADMIRAL trial.

Gilteritinib was approved by the FDA ( U.S. Food and Drug Administration ) in November 2018, for the treatment of adult patients who have relapsed or refractory AML that tests positive for an FLT3 mutation.
The FDA approval of gilteritinib was based on safety data and an interim analysis of the rate of response to Gilteritinib in the ADMIRAL trial; it was not based on a comparison of the efficacy of Gilteritinib relative to standard chemotherapy.

At AACR Annual Meeting researchers have presented the final analysis of the results from the ADMIRAL trial, including data showing that Gilteritinib is superior to standard chemotherapy, as measured by improved overall survival.

ADMIRAL was a randomized, phase III clinical trial designed to determine whether Gilteritinib improves survival for patients with relapsed or refractory FLT3-mutated AML compared with standard chemotherapy regimens, which included investigator’s choice of low-dose Cytarabine; Azacitidine; Mitoxantrone, Etoposide, and Cytarabine; and Fludarabine, Cytarabine, Granulocyte colony-stimulating factor, and Idarubicin.
Of the 371 patients enrolled in the clinical trial, 247 were randomly assigned to Gilteritinib and 124 to standard chemotherapy.

At the final analysis, patients assigned Gilteritinib were found to have a 36% reduction in risk of death compared with those assigned standard chemotherapy.
Median overall survival was 9.3 months for those assigned Gilteritinib vs 5.6 months for those assigned standard chemotherapy.
The 1-year survival rate was 37.1% in the Gilteritinib-treated group compared with 16.7% among those receiving standard chemotherapy.

The combined rate of complete remission and complete remission with partial hematologic recovery was 34.0% for those assigned Gilteritinib and 15.3% for those assigned standard chemotherapy.

The longest survival in the Gilteritinib arm was seen among patients who proceeded to transplant and then resumed Gilteritinib thereafter to prevent relapse, but unfortunately, long-term survival was very uncommon on either treatment arm.
In an effort to further improve long-term outcomes, clinical trials testing Gilteritinib in combination with other therapies for relapsed or refractory FLT3-mutated AML and testing Gilteritinib as frontline therapy for newly diagnosed patients have already been launched.

The main limitation of the study is that the standard front-line treatment for FLT3-mutated AML changed during enrollment to the ADMIRAL trial, because the FDA approved the FLT3-targeted therapeutic Midostaurin for this indication in April 2017.
Thus, a small minority of patients in both arms received prior FLT3-targeted therapy. It is possible that leukemias that relapsed after or were refractory to front-line treatment that included Midostaurin were less dependent on FLT3 for their growth and therefore had less likelihood of responding to Gilteritinib. ( Xagena )

Source: American Assocation for Cancer Research ( AACR ) Annual Meeting, 2019

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