Quizartinib for Newly Diagnosed FLT3 -Internal Tandem Duplication–Negative AML: The Randomized, Double-Blind, Placebo-Controlled, Phase II QUIWI Study
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
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.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco-25-01841
Authors: Pau Montesinos, Rebeca Rodríguez-Veiga, Juan Miguel Bergua, Jesús Lorenzo Algarra Algarra, Carmen Botella, Eduardo Rodríguez-Arbolí, Teresa Bernal, Mar Tormo, Maria Calbacho, Olga Salamero, Josefina Serrano, Victor Noriega, Juan Antonio López-López, Susana Vives, Jose Luis López-Lorenzo, Mercedes Colorado, Maria-Belén Vidriales, Raimundo García Boyero, Maria Teresa Olave, Pilar Herrera Puente, Olga Arce, Manuel Barrios, Maria Jose Sayas, Marta Polo, Maria Isabel Gómez-Roncero, Eva Barragán, Rosa Ayala, Carmen Chillón, Maria José Calasanz, Bruno Paiva, Blanca Boluda, Ignacio Casas-Avilés, Pilar Lloret-Madrid, Maria-José Sánchez, Carlos Rodríguez-Medina, Laida Cuevas, José Ángel Raposo-Puglia, M. Carmen Mateos, Matxalen Olivares, Carmen Martínez-Chamorro, Natalia Alonso, Sandra Suárez, Irene Sánchez-Vadillo, María Solé Rodríguez, Bernardo Javier González, Antonio Martínez-Francés, Rebeca Cuello, Alfonso Fernández, David Martínez-Cuadrón, Jorge Labrador, on behalf of the PETHEMA group, Víctor Noriega, Jesús Lorenzo Algarra Algarra, Carmen Botella, María José García Pérez, Susana Vives, Olga Salamero, Olga Arce, Jorge Labrador, Juan Miguel Bergua, Inmaculada Marchante Cepillo, Raimundo García Boyero, Josefina Serrano, Matxalen Olivares, Carlos Rodríguez-Medina, Antonio Romero Aguilar, María Solé Rodríguez, Juan Antonio López-López, María-José Sánchez, Carmen Martínez-Chamorro, Marta Polo, Pilar Herrera Puente, María Calbacho, José Luis López Lorenzo, Irene Sánchez-Vadillo, Alfonso Fernández Fernández, Manuel Barrios, Antonio Martínez-Francés, Teresa Bernal, M. Carmen Mateos, María Lourdes Amador Barciela, Maria-Belén Vidriales, Mercedes Colorado, Natalia Alonso, Adrian Mosquera, José Antonio Pérez Simón, Iryna Luts Khoroz, Bernardo Javier González, María Isabel Gómez Roncero, Rebeca Rodríguez-Veiga, Mar Tormo, Maria José Sayas, Rebeca Cuello, Sandra Suárez, Laida Cuevas Palomares, María Teresa Olave
Institutions: Hospital Universitari i Politècnic La Fe, Hospital San Pedro de Alcántara, Hospital General Universitario de Albacete, Hospital General Universitario de Alicante Doctor Balmis, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias, Hospital Clínico Universitario de Valencia, INCLIVA Health Research Institute, Hospital Universitario 12 De Octubre, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Universitario Reina Sofía, University of Córdoba, Complexo Hospitalario Universitario A Coruña, Complejo Hospitalario de Jaén, Institut Català d'Oncologia, Hospital Universitario Fundación Jiménez Díaz, Marqués de Valdecilla University Hospital, Instituto de Investigación Marqués de Valdecilla, Instituto de Investigación Biomédica de Salamanca, Hospital General Universitari de Castelló, Hospital Clínico Universitario Lozano Blesa, Hospital Universitario Ramón y Cajal, Hospital de Basurto, Hospital Regional Universitario de Málaga, Hospital Universitario Doctor Peset, Hospital Clínico San Carlos, Hospital Universitario de Toledo, Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, Hospital Universitario Lucus Augusti, Hospital Universitario de Gran Canaria Doctor Negrín, Hospital Universitario Araba, Hospital Universitario Puerta del Mar, Complejo Hospitalario de Navarra, Hospital de Galdakao, Hospital Universitario Quirónsalud Madrid, Complejo Hospitalario Universitario de Santiago, Instituto de Investigación Sanitaria de Santiago, University Hospital Complex Of Vigo, Hospital Universitario La Paz, Hospital Juan Ramón Jiménez, Hospital Universitario de Canarias, Santa Lucía University General Hospital, Hospital Clínico Universitario de Valladolid, Hospital Clínico Universitario Virgen de la Victoria, Hospital Universitario de Burgos
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funder: Daiichi Sankyo Europe
OpenAlex ID: W4415109808