Publication
Randomized phase III study of alisertib or investigator’s choice (selected single agent) in patients with relapsed or refractory peripheral T-cell lymphoma ¨
Publisher:
American Society of Clinical Oncology (ASCO)
Date:
10-03-2019
DOI:
10.1200/JCO.18.00899
Abstract: 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). 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/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. 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. In patients with relapsed/refractory PTCL, alisertib was not statistically significantly superior to the comparator arm.