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Results from Phase III Study of Gilteritinib Versus Chemotherapy Published in NEJM

Nichole Tucker
Published Online:6:42 PM, Mon November 4, 2019
Detailed results of the phase III ADMIRAL trial, which evaluated the use of gilteritinib (Xospata) in adult patients with FLT3 mutation–positive relapsed or refractory acute myeloid leukemia (AML), have been published in the New England Journal of Medicine and reaffirm the improved overall survival (OS) rate seen with gilteritinib compared with chemotherapy in these patients, according to a press release from Astellas Pharma Inc.1,2

In May 2019, the FDA updated the gilteritinib label to include the OS data.

The median OS in the gilteritinib arm was 9.3 months compared with 5.6 months in the group of patients who received chemotherapy (HR, 0.64; 95% CI, 0.49-0.83; P = .0001). Patients treated with gilteritinib also has a 2.8-month median event-free survival, which was 2.1 months longer than the patients in the chemotherapy group (HR, 0.79; 95% CI, 0.58-1.09).

With gilteritinib, 21% of patients achieved a complete remission, which was a significantly higher percentage than the 10.5% of patients who were treated with chemotherapy. Additionally, 34% of patients in the gilteritinib group had a complete remission with a full or partial hematologic recovery compared with 15.3% in the chemotherapy arm.

Treatment with gilteritinib also resulted in fewer grade 3 adverse events than with chemotherapy. The most common grade 3 or higher events were neutropenia (45.9%), anemia (40.7%), and thrombocytopenia (22.8%).

In the press release, a key trial investigator, Alexander Perl, MD, associate professor of Hematology-Oncology, Abramson Cancer Center, University of Pennsylvania, stated, “these data show that in a very high-risk leukemia population, single agent FLT3-targeted therapy leads to superior clinical outcomes compared to salvage chemotherapy. This is an important result for patients who previously had quite limited treatment options.”

Patients in this trial were randomized 2:1 to receive either treatment. The administered dose of gilteritinib was 120 mg per day (n = 247), which was given orally for 28 continuous days. Salvage chemotherapy was given also given for 28 days (n = 124), with the exception of low-dose cytarabine, which was administered either subcutaneously for 10 days or intravenously for 7 days. 

The primary endpoints of the study were OS and the percentage of patients who had a complete remission with either a full or partial hematologic recovery. The secondary endpoints were duration of event-free survival, duration of leukemia-free survival, percentage of patients with complete remission, duration of remission, percentage of participants with composite remission, percentage of subjects who achieved transfusion conversion and maintenance, and the number of patients with adverse events.

The study had eligibility criteria that included patients with AML or myelodysplastic syndrome (MDS) who had a FLT3 mutation in the bone marrow and were relapsed or refractory to first-line AML therapy. Patients were also required to have an ECOG performance status ≤2. The study excluded individuals who were diagnosed with acute promyelocytic leukemia or had BCR-ABL–positive leukemia. Patients also could not enroll in the trial if they had AML after chemotherapy for neoplasms, were in their second or later hematologic relapse, or had clinically active nervous system leukemia. The presence of comorbidities that could interfere with treatment also excluded some patients from the study.

Investigators continue to evaluate for the key endpoints in the phase III study which they plan to complete in December 2020. Astellas Pharma Inc. is also studying gilteritinib in comparison with other agents for the treatment of patients with FLT3-mutated AML.
  1. New England Journal of Medicine Publishes Results from Astellas’ Phase 3 ADMIRAL Trial of XOSPATA® (gilteritinib) in Adult Patients with FLT3 Mutation-Positive Relapsed/Refractory Acute Myeloid Leukemia [press release]. Tokyo, Japan: Astellas Pharma Inc.; October 31, 2019. https://bit.ly/2PBWb5C. Accessed November 1, 2019.
  2. Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med. 2019;381:1728-1740. doi: 10.1056/NEJMoa1902688.

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