The European Commission ( EC ) has approved the oral once-daily therapy Xospata ( Gilteritinib ) as a monotherapy for the treatment of adult patients with relapsed or refractory acute myeloid leukemia ( AML ) with a FLT3 mutation ( FLT3mut+ ).
Gilteritinib has the potential to improve treatment outcomes for AML patients with two forms of the most common mutation, FLT3 internal tandem duplication ( ITD ) and FLT3 tyrosine kinase domain ( TKD ) mutation.
This approval is based on results from the phase 3 ADMIRAL trial, which investigated Gilteritinib versus salvage chemotherapy in patients with relapsed or refractory FLT3mut+ acute myeloid leukemia.
Patients treated with Gilteritinib had significantly longer overall survival ( OS ) than those who received salvage chemotherapy.
Median overall survival for patients who received Gilteritinib was 9.3 months, compared to 5.6 months for patients who received salvage chemotherapy ( hazard ratio, HR= 0.64 [ 95% CI 0.49, 0.83 ], P=0.0004 ).
Rates of one-year survival were 37% for patients who received Gilteritinib, compared to 17% for patients who received salvage chemotherapy.
Acute myeloid leukemia is a rare cancer and patients with a FLT3 mutation have a particularly poor prognosis, with a median survival of less than six months following treatment with salvage chemotherapy.
The ADMIRAL trial was an open-label, multicenter, randomized study of Gilteritinib versus salvage chemotherapy in adult patients with FLT3mut+ who are refractory to or have relapsed after first-line AML therapy.
The co-primary endpoints of the trial were overall survival and CR/CRh rates [ complete response ( CR ) with incomplete count recovery ( CRh ) ]; overall survival, the primary endpoint at the trial's final analysis, was the basis of EC approval.
The study enrolled 371 patients with relapsed or refractory acute myeloid leukemia and FLT3mut+ present in bone marrow or whole blood.
Subjects were randomized in a 2:1 ratio to receive Gilteritinib ( 120 mg ) or salvage chemotherapy.
The most common adverse events across both treatment arms of the ADMIRAL trial were febrile neutropenia ( 43.7% ), anemia ( 43.4% ), and pyrexia ( 38.6% ).
Common grade greater than or equal to 3 adverse effects related to Gilteritinib were anemia ( 19.5% ), febrile neutropenia ( 15.4% ), thrombocytopenia ( 12.2% ), and decreased platelet count ( 12.2% ).
Adjusted for exposure duration, serious treatment-emergent adverse reactions per patient year were less common with Gilteritinib ( 7.1% ) than salvage chemotherapy ( 9.2% ). ( Xagena )
Source: Astellas, 2019