Quizartinib for Newly Diagnosed <i>FLT3</i> -Internal Tandem Duplication–Negative AML: The Randomized, Double-Blind, Placebo-Controlled, Phase II QUIWI Study
Pau Montesinos, Rebeca Rodríguez‐Veiga, Juan Bergua, Lorenzo Algarra, Carmen Botella, Eduardo Rodríguez‐Arbolí, Teresa Bernal, Mar Tormo, María Calbacho, Olga Salamero, Josefina Serrano, Víctor Noriega, Juan Antonio López, Susana Vives, José Luis López Lorenzo, Mercedes Colorado, María‐Belén Vídriales, Raimundo García Boyero, María Teresa Olave, Pilar Herrera Puente, Olga Arce, Manuel Barrios-García, María José Sayas-Lloris, Marta Polo Zarzuela, María Isabel Gómez-Roncero, Eva Barragán, Rosa Ayala, Carmen Chillón, Marı́a José Calasanz, Bruno Paiva, Blanca Boluda, Ignacio Casas-Avilés, Pilar Lloret Madrid, María‐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 Rodriguez, Bernardo Javier González González, Antonio Martínez‐Francés, Rebeca Cuello, Alfonso Madridejos 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
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.