Quizartinib for Newly Diagnosed FLT3-ITD-Negative Acute Myeloid Leukemia: The Randomized, Double-Blind, Placebo-Controlled, Phase 2 QUIWI Study
Montesinos P, Rodríguez-Veiga R, Bergua JM, Algarra Algarra JL, Botella C, Rodríguez-Arbolí E, Bernal T, Tormo M, Calbacho M, Salamero O, Serrano J, Noriega V, López-López JA, Vives S, López-Lorenzo JL, Colorado M, Vidriales MB, Boyero RG, Olave MT, Herrera P, Arce O, Barrios M, Sayas MJ, Polo M, Gómez-Roncero MI, Barragán E, Ayala R, Chillón C, Calasanz MJ, Paiva B, Boluda B, Casas-Avilés I, Lloret P, Sánchez MJ, Rodríguez-Medina C, Cuevas L, Raposo-Puglia JÁ, Mateos MC, Olivares M, Martínez-Chamorro C, Alonso N, Suárez S, Sánchez-Vadillo I, Rodríguez MS, González BJ, Martínez-Francés A, Cuello R, Fernández A, Martínez-Cuadrón D, Labrador J; PETHEMA group.
J Clin Oncol
Background: 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 FLT3, has shown early clinical activity as monotherapy in patients with relapsed/refractory FLT3-ITD-negative acute myeloid leukemia (AML). The phase 3 QuANTUM-First trial showed that quizartinib significantly prolonged survival vs 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 2, randomized, double-blind, placebo-controlled QUIWI trial enrolled patients aged 18-70 years with ND FLT3-ITD-negative (mutant-to-wild-type allelic ratio <0.03) AML. Patients were randomized 2:1 to receive standard induction and consolidation chemotherapy combined with either quizartinib 60 mg daily or placebo, followed by single-agent maintenance with quizartinib or placebo. The primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival (OS) and safety.
Results: Overall, 273 patients were randomized 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=0.046). Median OS was not reached and 29.3 months in the quizartinib and placebo arms, respectively (P=0.012); three-year OS rates were 60.8% and 45.7%. The most frequently reported adverse events (any grade) were fever, rash, diarrhea, and mucositis.
Conclusions: 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. ClinicalTrials.gov
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