Is Aurora A kinase inhibitor alisertib superior to standard treatment protocol for peripheral T-cell lymphoma?
Treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL) with the Aurora A kinase (AAK) inhibitor alisertib did not significantly improve outcomes compared with the use of investigator’s choice comparators, according to the results of a study published in Journal of Clinical Oncology.
The phase III study was stopped early at the recommendation of the independent data monitoring committee due to low probability of alisertib achieving progression-free survival (PFS) superiority.
“Although alisertib did not demonstrate superior efficacy over comparators, it showed activity and acceptable tolerability and safety in patients with relapsed/refractory PTCL, as well as positive trends in sensitivity analyses for progression-free survival, overall survival, duration of response, and time to progression,” wrote researchers led by Owen A. O’Connor, MD, PhD, of the Center for Lymphoid Malignancies.
Previous research has shown overexpression and upregulation of aurora kinases in PTCL, which supported AAK inhibition as a treatment approach. In this study, patients were randomly assigned to alisertib (n = 138) or to treatment with investigator’s choice (n = 133). Investigator-selected comparators were all single agents, including intravenous pralatrexate, intravenous gemcitabine, or intravenous romidepsin.
Patients assigned to alisertib had a median of four cycles of treatment and the median treatment duration was 20.8 weeks. In the comparator arm, there was a median of two cycles of treatment and a median treatment duration of 16.6 weeks.
At the time of study cessation, the overall response rate was 33% for patients assigned alisertib and 45% for the comparator arm (odds ratio [OR], 0.66; 95% CI, 0.33–1.08). Complete response rate was 18% with alisertib and 27% with comparators.
The median PFS was 115 days for alisertib compared with 104 days for the comparator arm (hazard ratio [HR], 0.87; 95% CI, 0.644–1.162). The 2-year overall survival was 35% for both study arms.
“The 0.87 HR that favored the alisertib arm, in which more patients had stable disease, indicated that alisertib actively controlled disease in patients with PTCL,” the researchers wrote. “A positive trend that favored alisertib was also observed for overall survival, duration of response, and time to progression, which further supported alisertib activity in this population.”
Patients assigned to alisertib had a longer mediation duration of response compared with the comparator arm (225 vs 172 days).
The majority of patients had at least one or more adverse event. More patients assigned to alisertib experienced the common adverse events of anemia (53% vs 34%) and neutropenia (47% vs 31%). However, a lower percentage of patients assigned to alisertib had adverse events that led to study drug discontinuation compared with the comparator treatments (9% vs 13%).
“One limitation of this study was that patients with a range of local diagnosis– based PTCL subtypes were enrolled, but 46 patients (17%) were subsequently identified by central expert review as lacking a protocol-eligible PTCL subtype-that is, no PTCL or inadequate tumor specimen,” the researchers wrote. “Therefore, the response-evaluable population was smaller than the safety population.”
Future studies should select appropriate patients population and confirm disease subtypes before dosing, according to the researchers.
“Additional studies are required to investigate whether alisertib provides greater benefit in a subgroup of patients with PTCL who responded poorly to comparator agents and the potential for treatment combinations of alisertib with novel agents,” they wrote.