Phase III LACEWING trial reports Gilteritinib plus azacitidine data in FLT3-mutant AML
核心洞察
Final phase III LACEWING results show gilteritinib plus azacitidine produced median overall survival of 9.82 months versus 9.23 months with azacitidine alone (HR 0.829; p=0.182).
Overall response rate was 70.2% with the combination versus 36.8% with azacitidine monotherapy (p<0.001), while gilteritinib monotherapy gave 72.7%.
Median overall survival favored the combination in FLT3 (搜索)-ITD patients without a TKD mutation and in those with a high FLT3-ITD allelic ratio, with more treatment-related adverse events on the combination.
Final analysis of the randomized, open-label phase III LACEWING study (NCT02752035) has been published in Haematologica by Wang et al. The trial compared gilteritinib plus azacitidine (n=104) with azacitidine (n=57) or gilteritinib (n=22) monotherapy in adults with newly diagnosed FLT3 (搜索)-mutated acute myeloid leukemia (搜索) who were ineligible for intensive chemotherapy. The primary endpoint was overall survival.
At a median follow-up of 30.1 months with the combination and not estimable with azacitidine, median overall survival was 9.82 months versus 9.23 months (hazard ratio 0.829; p=0.182). Median overall survival with gilteritinib monotherapy was 5.24 months. Overall response rate was 70.2% with gilteritinib plus azacitidine versus 36.8% with azacitidine (p<0.001) and 72.7% with gilteritinib alone.
In subgroup analyses, median overall survival was longer with the combination than with azacitidine in patients with FLT3 (搜索)-internal tandem duplication AML without a tyrosine kinase domain mutation (11.63 versus 8.87 months; nominal p=0.047) and in those with a high FLT3-ITD allelic ratio of at least 0.5 (11.89 versus 7.46 months; nominal p=0.016). Treatment-related adverse events were more frequent with the combination; the most common Grade 3 or higher events were neutropenia (24.3% versus 20.4%), febrile neutropenia (24.3% versus 7.4%), thrombocytopenia (18.4% versus 13.0%) and anemia (18.4% versus 16.7%).