Randomized phase III study of alisertib or investigator's choice (selected single agent) in patients with relapsed or refractory peripheral T-cell lymphoma Journal Article


Authors: O'Connor, O. A.; Özcan, M.; Jacobsen, E. D.; Roncero, J. M.; Trotman, J.; Demeter, J.; Masszi, T.; Pereira, J.; Ramchandren, R.; Beaven, A.; Caballero, D.; Horwitz, S. M.; Lennard, A.; Turgut, M.; Hamerschlak, N.; d'Amore, F. A.; Foss, F.; Kim, W. S.; Leonard, J. P.; Zinzani, P. L.; Chiattone, C. S.; Hsi, E. D.; Trümper, L.; Liu, H.; Sheldon-Waniga, E.; Ullmann, C. D.; Venkatakrishnan, K.; Leonard, E. J.; Shustov, A. R.; on behalf of the Lumiere Study Investigators
Article Title: Randomized phase III study of alisertib or investigator's choice (selected single agent) in patients with relapsed or refractory peripheral T-cell lymphoma
Abstract: PURPOSE: The 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 METHODS: Adult patients with relapsed/refractory PTCL-one or more prior therapy-were 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/m2 (once per week for 6 weeks; 7-week cycle), or intravenous gemcitabine 1,000 mg/m2 or intravenous romidepsin 14 mg/m2 (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. RESULTS: Between 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. CONCLUSION: In patients with relapsed/refractory PTCL, alisertib was not statistically significantly superior to the comparator arm.
Journal Title: Journal of Clinical Oncology
Volume: 37
Issue: 8
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2019-03-10
Start Page: 613
End Page: 623
Language: English
DOI: 10.1200/jco.18.00899
PUBMED: 30707661
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 April 2019 -- Source: Scopus
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  1. Steven M Horwitz
    364 Horwitz