Gilteritinib showed improvement in overall survival in patients with relapsed or refractory FLT3 mutation-positive acute myeloid leukemia compared with chemotherapy, meeting the primary end point of the phase 3 COMMODORE confirmatory trial.
Gilteritinib showed improvement in overall survival (OS) in patients with relapsed or refractory FLT3 mutation-positive acute myeloid leukemia (AML) compared with chemotherapy, meeting the primary end point of the phase 3 COMMODORE confirmatory trial.1
Results of the interim analysis were announced in a press release from Astellas Pharma Inc. Based on the positive OS result, the company has stopped trial enrollment and is allowing patients currently receiving chemotherapy in the study to switch to gilteritinib.
"In COMMODORE, patients receiving gilteritinib lived longer than those receiving salvage chemotherapy, confirming the overall survival benefit seen in the Phase 3 ADMIRAL trial," said Andrew Krivoshik, MD, PhD, senior vice president, and Global Therapeutic Area head, Oncology Development, in a press release. "For these patients, who have limited treatment options, the new findings provide additional evidence supporting gilteritinib as a treatment option."
COMMODORE, which is being conducted in the China, Malaysia, Russia, Singapore, and Thailand, is an open-label, randomized study. In addition to the primary end point, the study is evaluating even-free survival, complete remission, leukemia-free survival, duration of composite complete remission (CR), safety, and other response-related secondary end points.
The study aims to evaluate the use of gilteritinib in 276 patients who will be randomized 1:1 to either gilteritinib 120 mg or salvage chemotherapy.
To be eligible for inclusion, patients were required to have a diagnosis of primary or secondary AML, be refractory to or relapsed after first-line AML therapy, and test positive for a FLT3 mutation. At study entry, patients were also required to have an ECOG performance status of ≤ 2, be eligible to receive preselected salvage chemotherapy, have adequate laboratory values, and be suitable for administration of gilteritinib.
Data from COMMODORE build upon prior positive results observed with gilteritinib as treatment of patients with relapsed/refractory FLT3-mutated AML in the ADMIRAL clinical trial (NCT02421939). Gilteritinib was compared with chemotherapy in the study and achieved a significantly longer survival and increased rate of remissions over chemotherapy. The study included a total of 371 patients. In a 2:1 randomization, 247 patients were treated with gilteritinib and 124 were treated with salvage chemotherapy. Gilteritinib showed a median OS of 9.3 months versus 5.6 months with chemotherapy (HR, 0.64; 95% CI, 0.49 to 0.83; P <.001. In addition, the median EFS observed with gilteritinib was 2.8 months versus 0.7 months in the chemotherapy group (HR, 0.79; 95% CI, 0.58 to 1.09).2
Response data from the ADMIRAL study showed that 34.0% of patients treated with gilteritinib achieved a CR with full or partial hematologic recovery compared with only 15.3% of the chemotherapy arm (risk difference, 18.6 percentage points; 95% CI, 9.8 to 27.4). Also, the CR rate in the gilteritinib arm was 21.1% versus 10.5% in the chemotherapy arm (risk difference, 10.6 percentage points; 95% CI, 2.8 to 18.4).
Safety results for gilteritinib in FLT3-positive AML were also shown in the ADMIRAL study. There was a lower frequency of grade 3 or higher adverse events in the gilteritinib arm compared with the chemotherapy. In addition, the most common grade 3 or higher AEs observed with gilteritinib treatment were febrile neutropenia (45.9%), anemia (40.7%), and thrombocytopenia (22.8%).
In other prior clinical trials of gilteritinib, the toxicities observed with the agents included alanine aminotransferase increased (25.4%), aspartate aminotransferase increased (24.5%), anemia (20.1%), thrombocytopenia (13.5%), febrile neutropenia (12.5%), platelet count decreased (12.2%), diarrhea (12.2%), nausea (11.3%), blood alkaline phosphatase increased (11%), fatigue (10.3%), white blood cell count decreased (10%), and blood creatine phosphokinase increased (10%). Fatal differentiation syndrome has occurred with gilteritinib, as have serious events like electrocardiogram QT prolonged (0.9%) and posterior reversible encephalopathy syndrome (0.3%).
1. Astellas' XOSPATA® (gilteritinib) meets overall survival endpoint in COMMODORE trial of patients with relapsed or refractory acute myeloid leukemia with a FLT3 mutation. News release. March 30, 2021. Accessed March 30, 2021. https://bit.ly/2PI6Bm6
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(18):1728-1740. doi: 10.1056/NEJMoa1902688