Alisertib vs Investigator’s Choice in Relapsed or Refractory Peripheral T-Cell Lymphoma
In the phase III Lumiere trial reported in the Journal of Clinical Oncology, O’Connor et al found that the Aurora A kinase inhibitor alisertib did not improve outcomes vs investigator’s choice of single-agent treatment in relapsed or refractory peripheral T-cell lymphoma (PTCL).
Study Details
The open-label trial included 271 adult patients who had received ≥ 1 prior therapy from 105 sites in 27 countries. Patients were randomly assigned between May 2012 and October 2014 to receive oral alisertib 50 mg two times per day on days 1 to 7 of 21-day cycles (n = 138) or investigator's choice of intravenous (IV) pralatrexate, IV gemcitabine, or IV romidepsin. Responses were assessed on independent central review.
Primary endpoints were overall response rate and progression-free survival.
Treatment Outcomes
On the recommendation of the independent data monitoring committee, enrollment was stopped early due to the low probability of alisertib achieving progression-free survival superiority with full enrollment.
The overall response rates were 33% in the alisertib group vs 45% in the comparator group (odds ratio = 0.60, 95% confidence interval [CI] = 0.33–1.08). Response rates were 35% in 23 patients receiving gemcitabine, 43% in 51 receiving pralatrexate, and 61% in 18 receiving romidepsin.
Median progression-free survival was 115 days vs 104 days (hazard ratio = 0.87, 95% CI = 0.637–1.178). Median progression-free survival was 57 days with gemcitabine, 101 days with pralatrexate, and 242 days with romidepsin. Overall survival at 2 years was 35% in both groups.
Adverse Events
Grade ≥ 3 adverse events occurred in 85% of the alisertib group vs 79% of the comparator group, with the most common being neutropenia (43% vs 25%), thrombocytopenia (29% vs 27%), and anemia (33% vs 11%). Adverse events led to treatment discontinuation in 9% vs 14% of patients. Five deaths were considered treatment-related, including 3 in the alisertib group and 2 in the comparator group.
The investigators concluded, “In patients with relapsed/refractory PTCL, alisertib was not statistically significantly superior to the comparator arm.”
Owen A. O’Connor, MD, PhD, of the Center for Lymphoid Malignancies, Columbia University Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. The study authors' full disclosures can be found at jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
