Publication:
Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes.

dc.contributor.authorGarcia-Manero, Guillermo
dc.contributor.authorSantini, Valeria
dc.contributor.authorAlmeida, Antonio
dc.contributor.authorPlatzbecker, Uwe
dc.contributor.authorJonasova, Anna
dc.contributor.authorSilverman, Lewis R
dc.contributor.authorFalantes, Jose
dc.contributor.authorReda, Gianluigi
dc.contributor.authorBuccisano, Francesco
dc.contributor.authorFenaux, Pierre
dc.contributor.authorBuckstein, Rena
dc.contributor.authorDiez Campelo, Maria
dc.contributor.authorLarsen, Stephen
dc.contributor.authorValcarcel, David
dc.contributor.authorVyas, Paresh
dc.contributor.authorGiai, Valentina
dc.contributor.authorOlíva, Esther Natalie
dc.contributor.authorShortt, Jake
dc.contributor.authorNiederwieser, Dietger
dc.contributor.authorMittelman, Moshe
dc.contributor.authorFianchi, Luana
dc.contributor.authorLa Torre, Ignazia
dc.contributor.authorZhong, Jianhua
dc.contributor.authorLaille, Eric
dc.contributor.authorLopes de Menezes, Daniel
dc.contributor.authorSkikne, Barry
dc.contributor.authorBeach, C L
dc.contributor.authorGiagounidis, Aristoteles
dc.date.accessioned2023-02-09T10:47:01Z
dc.date.available2023-02-09T10:47:01Z
dc.date.issued2021-03-25
dc.description.abstractTreatment options are limited for patients with lower-risk myelodysplastic syndromes (LR-MDS). This phase III, placebo-controlled trial evaluated CC-486 (oral azacitidine), a hypomethylating agent, in patients with International Prognostic Scoring System LR-MDS and RBC transfusion-dependent anemia and thrombocytopenia. Patients were randomly assigned 1:1 to CC-486 300-mg or placebo for 21 days/28-day cycle. The primary end point was RBC transfusion independence (TI). Two hundred sixteen patients received CC-486 (n = 107) or placebo (n = 109). The median age was 74 years, median platelet count was 25 × 109/L, and absolute neutrophil count was 1.3 × 109/L. In the CC-486 and placebo arms, 31% and 11% of patients, respectively, achieved RBC-TI (P = .0002), with median durations of 11.1 and 5.0 months. Reductions of ≥ 4 RBC units were attained by 42.1% and 30.6% of patients, respectively, with median durations of 10.0 and 2.3 months, and more CC-486 patients had ≥ 1.5 g/dL hemoglobin increases from baseline (23.4% v 4.6%). Platelet hematologic improvement rate was higher with CC-486 (24.3% v 6.5%). Underpowered interim overall survival analysis showed no difference between CC-486 and placebo (median, 17.3 v 16.2 months; P = .96). Low-grade GI events were the most common adverse events in both arms. In the CC-486 and placebo arms, 90% and 73% of patients experienced a grade 3-4 adverse event. Overall death rate was similar between arms, but there was an imbalance in deaths during the first 56 days (CC-486, n = 16; placebo, n = 6), most related to infections; the median pretreatment absolute neutrophil count for the 16 CC-486 patients was 0.57 × 109/L. CC-486 significantly improved RBC-TI rate and induced durable bilineage improvements in patients with LR-MDS and high-risk disease features. More early deaths occurred in the CC-486 arm, most related to infections in patients with significant pretreatment neutropenia. Further evaluation of CC-486 in MDS is needed.
dc.identifier.doi10.1200/JCO.20.02619
dc.identifier.essn1527-7755
dc.identifier.pmcPMC8099416
dc.identifier.pmid33764805
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099416/pdf
dc.identifier.unpaywallURLhttps://ascopubs.org/doi/pdfdirect/10.1200/JCO.20.02619
dc.identifier.urihttp://hdl.handle.net/10668/17400
dc.issue.number13
dc.journal.titleJournal of clinical oncology : official journal of the American Society of Clinical Oncology
dc.journal.titleabbreviationJ Clin Oncol
dc.language.isoen
dc.organizationHospital Universitario Virgen del Rocío
dc.page.number1426-1436
dc.pubmedtypeClinical Trial, Phase III
dc.pubmedtypeJournal Article
dc.pubmedtypeMulticenter Study
dc.pubmedtypeRandomized Controlled Trial
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.meshAdministration, Oral
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshAzacitidine
dc.subject.meshFemale
dc.subject.meshFollow-Up Studies
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshMyelodysplastic Syndromes
dc.subject.meshPrognosis
dc.subject.meshProspective Studies
dc.subject.meshSurvival Rate
dc.titlePhase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number39
dspace.entity.typePublication

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