Gilteritinib/Azacitidine Fails to Significantly Improve OS in Newly Diagnosed FLT3+ AML

Andrew Krivoshik, MD, PhD

The addition of gilteritinib (Xospata) to azacitidine failed to significantly improve overall survival (OS) vs azacitidine alone in patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) who were not eligible for intensive induction chemotherapy, failing to meet the primary end point of the LACEWING trial (NCT02752035).¹

Based on these data, an independent data monitoring committee had recommended that the study be terminated for futility, as the findings are unlikely to demonstrate a statistically significant benefit in OS. Based on the recommendation, Astellas Pharma Inc. has stopped enrollment to the trial and announced that they will be assessing the data for other action, as required.

“Although we are disappointed by the primary outcome of LACEWING, we are conducting a thorough review of the data and plan to share detailed results at a later date,” Andrew Krivoshik, MD, PhD, senior vice president and oncology therapeutic area head of Astellas, stated in a press release.

In the open-label, multicenter, phase 3 trial, investigators set out to examine gilteritinib/azacitidine vs single-agent azacitidine in about 250 patients with newly diagnosed FLT3-mutated AML who were determined to be ineligible for frontline intensive induction chemotherapy.

To be eligible for enrollment, patients had to have a diagnosis of previously treated AML per World Health Organization classification, have a FLT3 mutation in the bone marrow or whole blood as detected by central laboratory analysis and they had to be ineligible for intensive induction chemotherapy.²

Moreover, they needed to have serum aspartate aminotransferase and alanine aminotransferase of less than or equal to 3.0 x institutional upper limit of normal (ULN), serum total bilirubin of less than or equal to 1.5 x institutional ULN, serum potassium that was greater than or equal to institutional lower limit of normal (LLN), and serum magnesium of greater than or equal to institutional LLN. Repletion of potassium and magnesium levels during the screening period of the trial was permitted.

In the trial, participants were randomized 2:1 to receive gilteritinib plus azacitidine or azacitidine alone. Patients entered a screening period of up to 2 weeks before treatment initiation; they then received azacitidine for 7 days, on days 1-7, for each 28-day treatment cycle.

The primary end point of the trial was OS, which was defined as the time from the date of randomization until the date of death from any cause. Secondary objectives comprised event-free survival, best response, complete remission, composite complete remission, and complete remission with partial hematologic recovery.

“These results do not affect other ongoing gilteritinib trials. We remain committed to our comprehensive program investigating gilteritinib across a wide range of [patients with] AML with a positive FLT3 mutation, building on gilteritinib’s earlier, positive data in patients with relapsed or refractory FLT3 mutation–positive AML,” added Krivoshik.

References

1. Astellas report Xospata (gilteritinib) in combination with azacitidine did not meet endpoint of overall survival in newly diagnosed FLT3 mutation-positive acute myeloid leukemia patients ineligible for intensive induction chemotherapy. News release. Astellas Pharma Inc. December 21, 2020. Accessed December 21, 2020. http://prn.to/3h98q5j.
2. A study of ASP2215 (gilteritinib) by itself, ASP2215 combined with azacitidine or azacitidine by itself to treat adult patients who have recently been diagnosed with acute myeloid leukemia with a FLT3 gene mutation and who cannot receive standard chemotherapy. ClinicalTrials.gov. Updated December 19, 2020. Accessed December 21, 2020. https://clinicaltrials.gov/ct2/show/NCT02752035.