Publication: Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes.
dc.contributor.author | Garcia-Manero, Guillermo | |
dc.contributor.author | Santini, Valeria | |
dc.contributor.author | Almeida, Antonio | |
dc.contributor.author | Platzbecker, Uwe | |
dc.contributor.author | Jonasova, Anna | |
dc.contributor.author | Silverman, Lewis R | |
dc.contributor.author | Falantes, Jose | |
dc.contributor.author | Reda, Gianluigi | |
dc.contributor.author | Buccisano, Francesco | |
dc.contributor.author | Fenaux, Pierre | |
dc.contributor.author | Buckstein, Rena | |
dc.contributor.author | Diez Campelo, Maria | |
dc.contributor.author | Larsen, Stephen | |
dc.contributor.author | Valcarcel, David | |
dc.contributor.author | Vyas, Paresh | |
dc.contributor.author | Giai, Valentina | |
dc.contributor.author | Olíva, Esther Natalie | |
dc.contributor.author | Shortt, Jake | |
dc.contributor.author | Niederwieser, Dietger | |
dc.contributor.author | Mittelman, Moshe | |
dc.contributor.author | Fianchi, Luana | |
dc.contributor.author | La Torre, Ignazia | |
dc.contributor.author | Zhong, Jianhua | |
dc.contributor.author | Laille, Eric | |
dc.contributor.author | Lopes de Menezes, Daniel | |
dc.contributor.author | Skikne, Barry | |
dc.contributor.author | Beach, C L | |
dc.contributor.author | Giagounidis, Aristoteles | |
dc.date.accessioned | 2023-02-09T10:47:01Z | |
dc.date.available | 2023-02-09T10:47:01Z | |
dc.date.issued | 2021-03-25 | |
dc.description.abstract | Treatment 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.doi | 10.1200/JCO.20.02619 | |
dc.identifier.essn | 1527-7755 | |
dc.identifier.pmc | PMC8099416 | |
dc.identifier.pmid | 33764805 | |
dc.identifier.pubmedURL | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099416/pdf | |
dc.identifier.unpaywallURL | https://ascopubs.org/doi/pdfdirect/10.1200/JCO.20.02619 | |
dc.identifier.uri | http://hdl.handle.net/10668/17400 | |
dc.issue.number | 13 | |
dc.journal.title | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | |
dc.journal.titleabbreviation | J Clin Oncol | |
dc.language.iso | en | |
dc.organization | Hospital Universitario Virgen del Rocío | |
dc.page.number | 1426-1436 | |
dc.pubmedtype | Clinical Trial, Phase III | |
dc.pubmedtype | Journal Article | |
dc.pubmedtype | Multicenter Study | |
dc.pubmedtype | Randomized Controlled Trial | |
dc.pubmedtype | Research Support, Non-U.S. Gov't | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.accessRights | open access | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject.mesh | Administration, Oral | |
dc.subject.mesh | Adult | |
dc.subject.mesh | Aged | |
dc.subject.mesh | Aged, 80 and over | |
dc.subject.mesh | Azacitidine | |
dc.subject.mesh | Female | |
dc.subject.mesh | Follow-Up Studies | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Male | |
dc.subject.mesh | Middle Aged | |
dc.subject.mesh | Myelodysplastic Syndromes | |
dc.subject.mesh | Prognosis | |
dc.subject.mesh | Prospective Studies | |
dc.subject.mesh | Survival Rate | |
dc.title | Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes. | |
dc.type | research article | |
dc.type.hasVersion | VoR | |
dc.volume.number | 39 | |
dspace.entity.type | Publication |
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