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Clinical Trial
. 2026 Jan;44(1):42-53.
doi: 10.1200/JCO-25-01841. Epub 2025 Oct 13.

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

Pau Montesinos  1 , Rebeca Rodríguez-Veiga  1 , Juan Miguel Bergua  2 , Jesús Lorenzo Algarra Algarra  3 , Carmen Botella  4 , Eduardo Rodríguez-Arbolí  5 , Teresa Bernal  6 , Mar Tormo  7 , Maria Calbacho  8 , Olga Salamero  9 , Josefina Serrano  10 , Victor Noriega  11 , Juan Antonio López-López  12 , Susana Vives  13 , Jose Luis López-Lorenzo  14 , Mercedes Colorado  15 , Maria-Belén Vidriales  16 , Raimundo García Boyero  17 , Maria Teresa Olave  18 , Pilar Herrera Puente  19 , Olga Arce  20 , Manuel Barrios  21 , Maria Jose Sayas  22 , Marta Polo  23 , Maria Isabel Gómez-Roncero  24 , Eva Barragán  1 , Rosa Ayala  8 , Carmen Chillón  16 , Maria José Calasanz  25 , Bruno Paiva  25 , Blanca Boluda  1 , Ignacio Casas-Avilés  2 , Pilar Lloret-Madrid  1 , Maria-José Sánchez  26 , Carlos Rodríguez-Medina  27 , Laida Cuevas  28 , José Ángel Raposo-Puglia  29 , M Carmen Mateos  30 , Matxalen Olivares  31 , Carmen Martínez-Chamorro  32 , Natalia Alonso  33 , Sandra Suárez  34 , Irene Sánchez-Vadillo  35 , María Solé Rodríguez  36 , Bernardo Javier González  37 , Antonio Martínez-Francés  38 , Rebeca Cuello  39 , Alfonso Fernández  40 , David Martínez-Cuadrón  1 , Jorge Labrador  41 ; PETHEMA group; PETHEMA Group
Collaborators, Affiliations
Clinical Trial

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

Pau Montesinos et al. J Clin Oncol. 2026 Jan.

Erratum in

  • Erratum: Quizartinib for Newly Diagnosed FLT3-Internal Tandem Duplication-Negative AML: The Randomized, Double-Blind, Placebo-Controlled, Phase II 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. Montesinos P, et al. J Clin Oncol. 2026 Jan 10;44(2):134. doi: 10.1200/JCO-25-02762. Epub 2025 Dec 1. J Clin Oncol. 2026. PMID: 41325561 No abstract available.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT04107727.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Figures

FIG 1.
FIG 1.
CONSORT study design and patient disposition. allo-HCT, allogeneic hematopoietic cell transplantation; FLT3, FMS-like tyrosine kinase 3; ITD, internal tandem duplication; ITT, intention-to-treat.
FIG 2.
FIG 2.
(A) EFS and (B) OS in patients treated with quizartinib or placebo. EFS, event-free survival; HR, hazard ratio; NR, not reached; OS, overall survival.
FIG 3.
FIG 3.
(A) OS in patients younger than 60 years; (B) OS in patients age 60 years and older; (C) OS in patients who underwent allo-HCT; and (D) OS in patients who did not undergo allo-HCT. allo-HCT, allogeneic hematopoietic cell transplantation; HR, hazard ratio; NR, not reached; OS, overall survival.
See this image and copyright information in PMC

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