Confirmatory Trial of Gilteritinib Meets Primary End Point of Improving OS in Relapsed/Refractory FLT3+ AML

Treatment with gilteritinib, compared with salvage chemotherapy, improved overall survival in patients with relapsed/refractory FLT3 mutation–positive acute myeloid leukemia, according to a planned interim analysis of a phase 3 trial.

A phase 3 confirmatory trial designed to evaluate gilteritinib (Xospata) met its primary end point of improving overall survival (OS) compared with chemotherapy in patients with relapsed/refractory FLT3 mutation–positive acute myeloid leukemia (AML), according to a planned interim analysis reported by Astellas Pharma Inc., the agent’s manufacturer.1

The open-label, randomized COMMODORE trial (NCT03182244) evaluated gilteritinib compared with salvage chemotherapy in adult patients who have relapsed or refractory AML. Patients were randomized 1:1 to receive either 120 mg gilteritinib or salvage chemotherapy.

OS served as the primary end points, while secondary end points include safety, event-free survival (EFS), and complete remission (CR).

“In COMMODORE, patients receiving gilteritinib lived longer than those receiving salvage chemotherapy, confirming the overall survival benefit seen in the phase 3 ADMIRAL trial,” Andrew Krivoshik, MD, PhD, senior vice president and global therapeutic area head of oncology development at Astellas, said in a press release. “For these patients, who have limited treatment options, the new findings provide additional evidence supporting gilteritinib as a treatment option.”

The company also noted that it has stopped enrollment in the trial. Moreover, patients in the chemotherapy arm will be offered the opportunity to switch arms and receive gilteritinib.

In the previously-reported, open-label, multicenter, randomized phase 3 ADMIRAL trial (NCT02421939), investigators randomized 371 adult patients with relapsed/refractory FLT3-positive AML 2:1 to receive either gilteritinib (n = 247) or salvage chemotherapy (n = 124).2

The co-primary end points of the ADMIRAL trial were OS and CR with full or partial hematologic recovery (CRh). Secondary end points included EFS and the percentage of patients who had complete remission.

Gilteritinib demonstrated significantly longer median OS compared with chemotherapy (9.3 months vs 5.6 months, respectively; HR, 0.64; 95% CI, 0.49-0.83; P <.001), as well as improved EFS (2.8 months vs 0.7 months; HR, 0.79; 95% CI, 0.58-1.09). In addition, a larger proportion of patients experienced CRh (34.0% vs 15.3%, respectively; risk difference, 18.6 percentage points; 95% CI, 9.8-27.4) and CR (21.1% vs 10.5%; risk difference, 10.6 percentage points; 95% CI, 2.8-18.4) with gilteritinib compared with chemotherapy.

In addition, the study showed that grade 3 or higher adverse events (AEs) occurred less frequently with gilteritinib compared with chemotherapy. The most common grade 3 or higher AEs in the gilteritinib group were febrile neutropenia (45.9%), anemia (40.7%), and thrombocytopenia (22.8%).

“Treatment options for patients with relapsed or refractory FLT3-mutated AML are largely limited to various salvage chemotherapy regimens, and there is no consensus regarding an approach,” the investigators of the ADMIRAL trial concluded. “We found that in this population of patients, gilteritinib resulted in superior overall survival and percentages of remission as compared with salvage chemotherapy.”


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. Astellas Pharma Inc. Published March 29, 2021. Accessed March 30, 2021.

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