Phase III LACEWING trial: Gilteritinib + azacitidine vs monotherapy in ND FLT3m AML

Results from the final analysis of the randomized, open-label, phase III LACEWING study (NCT02752035) evaluating gilteritinib + azacitidine (Aza; n = 104) vs Aza (n = 57) or gilteritinib (n = 22) monotherapy in adults with newly diagnosed (ND) FLT3-mutated (FLT3m) acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC) were published in Haematologica by Wang et al. The primary endpoint was overall survival (OS).

Key data: At a median follow-up of 30.1 months with gilteritinib + Aza and not estimable (NE) with Aza, median OS was 9.82 months vs 9.23 months, respectively (hazard ratio [HR], 0.829; p = 0.182). Median OS with gilteritinib was 5.24 months, with a NE median follow-up. The overall response rate (ORR) was 70.2% with gilteritinib + Aza vs 36.8% with Aza (p < 0.001) and 72.7% with gilteritinib. In subgroup analysis, median OS was longer with gilteritinib + Aza vs Aza in patients with FLT3-internal tandem duplication (ITD) AML without a tyrosine kinase domain (TKD) mutation (11.63 months vs 8.87 months; nominal p = 0.047) and in those with a high FLT3-ITD allelic ratio (≥0.5; 11.89 months vs 7.46 months; nominal p = 0.016). Treatment-related adverse events (TRAEs) were more frequent with gilteritinib + Aza vs Aza; the most common Grade ≥3 TRAEs were neutropenia (24.3% vs 20.4%), febrile neutropenia (24.3% vs 7.4%), thrombocytopenia (18.4% vs 13.0%), and anemia (18.4% vs 16.7%). 

Key learning: In this study, gilteritinib + Aza did not improve median OS vs Aza in patients with ND FLT3m AML ineligible for IC. Nominal OS benefits were observed in patients with FLT3-ITD without a TKD mutation and in those with a high FLT3-ITD allelic ratio, but these findings require further evaluation.