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A phase 3 trial of azacitidine versus a semi‐intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia
Author(s) -
Vives Susana,
MartínezCuadrón David,
Bergua Burgues Juan,
Algarra Lorenzo,
Tormo Mar,
MartínezSánchez María Pilar,
Serrano Josefina,
Herrera Pilar,
Ramos Fernando,
Salamero Olga,
Lavilla Esperanza,
LópezLorenzo José L.,
Gil Cristina,
Vidriales Belén,
Falantes Jose F.,
Serrano Alfons,
Labrador Jorge,
Sayas María J.,
Foncillas María Á.,
Amador Barciela María L.,
Olave María Teresa,
Colorado Mercedes,
Gascón Adriana,
Fernández María Á.,
Simiele Adriana,
PérezEncinas Manuel M.,
RodríguezVeiga Rebeca,
García Olga,
MartínezLópez Joaquín,
Barragán Eva,
Paiva Bruno,
Sanz Miguel Á.,
Montesinos Pau
Publication year - 2021
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.33403
Subject(s) - medicine , cytarabine , fludarabine , regimen , myeloid leukemia , azacitidine , randomized controlled trial , filgrastim , surgery , gastroenterology , neutropenia , chemotherapy , cyclophosphamide , biochemistry , gene expression , chemistry , dna methylation , gene
BACKGROUND Options to treat elderly patients (≥65 years old) newly diagnosed with acute myeloid leukemia (AML) include intensive and attenuated chemotherapy, hypomethylating agents with or without venetoclax, and supportive care. This multicenter, randomized, open‐label, phase 3 trial was designed to assess the efficacy and safety of a fludarabine, cytarabine, and filgrastim (FLUGA) regimen in comparison with azacitidine (AZA). METHODS Patients (n = 283) were randomized 1:1 to FLUGA (n = 141) or AZA (n = 142). Response was evaluated after cycles 1, 3, 6, and 9. Measurable residual disease (MRD) was assessed after cycle 9. When MRD was ≥0.01%, patients continued with the treatment until relapse or progressive disease. Patients with MRD < 0.01% suspended treatment to enter the follow‐up phase. RESULTS The complete remission (CR) rate after 3 cycles was significantly better in the FLUGA arm (18% vs 9%; P = .04), but the CR/CR with incomplete recovery rate at 9 months was similar (33% vs 29%; P = .41). There were no significant differences between arms in early mortality at 30 or 60 days. Hematologic toxicities were more frequent with FLUGA, especially during induction. The 1‐year overall survival (OS) rate and the median OS were superior with AZA versus FLUGA: 47% versus 27% and 9.8 months (95% confidence interval [CI], 5.6‐14 months) versus 4.1 months (95% CI, 2.7‐5.5 months; P = .005), respectively. The median event‐free survival was 4.9 months (95% CI, 2.8‐7 months) with AZA and 3 months (95% CI, 2.5‐3.5 months) with FLUGA ( P = .001). CONCLUSIONS FLUGA achieved more remissions after 3 cycles, but the 1‐year OS rate was superior with AZA. However, long‐term outcomes were disappointing in both arms (3‐year OS rate, 10% vs 5%). This study supports the use of an AZA backbone for future combinations in elderly patients with AML.