Randomized Phase III Study of Alisertib or Investigator's Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma

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art_O'CONNOR_Randomized_Phase_III_Study_of_Alisertib_or_Investigators_2019.PDF (763.5 KB)
Citações na Scopus
101
Tipo de produção
article
Data de publicação
2019
Editora
AMER SOC CLINICAL ONCOLOGY
DOI
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Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
O'CONNOR, Owen A.
OZCAN, Muhit
JACOBSEN, Eric D.
RONCERO, Josep M.
TROTMAN, Judith
DEMETER, Judit
MASSZI, Tamas
RAMCHANDREN, Radhakrishnan
BEAVEN, Anne
Autor de Grupo de pesquisa
Lumiere Study Investigators
Editores
Coordenadores
Organizadores
Citação
JOURNAL OF CLINICAL ONCOLOGY, v.37, n.8, p.613-+, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
PURPOSEThe aim of this open-label, first-in-setting, randomized phase III trial was to evaluate the efficacy of alisertib, an investigational Aurora A kinase inhibitor, in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL).PATIENTS AND METHODSAdult patients with relapsed/refractory PTCLone or more prior therapywere randomly assigned 1:1 to receive oral alisertib 50 mg two times per day (days 1 to 7; 21-day cycle) or investigator-selected single-agent comparator, including intravenous pralatrexate 30 mg/m(2) (once per week for 6 weeks; 7-week cycle), or intravenous gemcitabine 1,000 mg/m(2) or intravenous romidepsin 14 mg/m(2) (days 1, 8, and 15; 28-day cycle). Tumor tissue (disease subtype) and imaging were assessed by independent central review. Primary outcomes were overall response rate and progression-free survival (PFS). Two interim analyses and one final analysis were planned.RESULTSBetween May 2012 and October 2014, 271 patients were randomly assigned (alisertib, n = 138; comparator, n = 133). Enrollment was stopped early on the recommendation of the independent data monitoring committee as a result of the low probability of alisertib achieving PFS superiority with full enrollment. Centrally assessed overall response rate was 33% for alisertib and 45% for the comparator arm (odds ratio, 0.60; 95% CI, 0.33 to 1.08). Median PFS was 115 days for alisertib and 104 days for the comparator arm (hazard ratio, 0.87; 95% CI, 0.637 to 1.178). The most common adverse events were anemia (53% of alisertib-treated patients v 34% of comparator-treated patients) and neutropenia (47% v 31%, respectively). A lower percentage of patients who received alisertib (9%) compared with the comparator (14%) experienced events that led to study drug discontinuation. Of 26 on-study deaths, five were considered treatment related (alisertib, n = 3 of 11; comparator, n = 2 of 15). Two-year overall survival was 35% for each arm.CONCLUSIONIn patients with relapsed/refractory PTCL, alisertib was not statistically significantly superior to the comparator arm.
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URI
https://observatorio.fm.usp.br/handle/OPI/31604
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - LIM/31
Artigos e Materiais de Revistas Científicas - ODS/03