Quizartinib for Newly Diagnosed FLT3 -Internal Tandem Duplication–Negative AML: The Randomized, Double-Blind, Placebo-Controlled, Phase II QUIWI Study

PURPOSE Quizartinib, an oral, selective, second-generation, type-II FMS-like tyrosine kinase 3 (FLT3) inhibitor with high binding affinity to internal tandem duplication (ITD) and wild-type (WT) FLT3, has shown early clinical activity as monotherapy in patients with relapsed/refractory FLT3 -ITD–negative AML. The phase III QuANTUM-First trial showed that quizartinib significantly prolonged survival versus placebo when added to standard chemotherapy, followed by single-agent maintenance, in patients with newly diagnosed (ND) FLT3- ITD–positive AML. We investigated the safety and efficacy of quizartinib in patients with ND FLT3 -ITD–negative AML. METHODS The phase II, randomized, double-blind, placebo-controlled QUIWI trial enrolled patients age 18-70 years with ND FLT3 -ITD–negative (mutant-to-WT allelic ratio <0.03) AML. Patients were randomly assigned 2:1 to receive standard induction and consolidation chemotherapy combined with either quizartinib 60 mg once daily or placebo, followed by single-agent maintenance with quizartinib or placebo. The primary end point was event-free survival (EFS). Secondary end points included overall survival (OS) and safety. RESULTS Overall, 273 patients were randomly assigned to quizartinib (n = 180) or placebo (n = 93). At data cutoff, median EFS was 20.4 months and 9.9 months in the quizartinib and placebo arms, respectively ( P = .046). Median OS was not reached and 29.3 months in the quizartinib and placebo arms, respectively ( P = .012); 3-year OS rates were 60.8% and 45.7%. The most frequently reported adverse events (any grade) were fever, rash, diarrhea, and mucositis. CONCLUSION The addition of quizartinib to standard chemotherapy was associated with significantly longer EFS and OS than placebo in patients with ND FLT3 -ITD–negative AML.