Phase II Study Shows Activity of Aurora A Kinase Inhibitor Alisertib in Relapsed/Refractory Peripheral T-Cell Lymphoma
In a phase II Intergroup trial (SWOG 1108) reported in the Journal of Clinical Oncology, Barr et al found that the aurora A kinase inhibitor alisertib produced responses in patients with relapsed/refractory peripheral T-cell non-Hodgkin lymphoma. Aurora A kinase is upregulated in highly proliferative lymphomas.
Study Details
In the study, 37 patients with relapsed/refractory peripheral T-cell lymphoma or transformed mycosis fungoides received alisertib 50 mg twice a day for 7 days in 21-day cycles. Patients had peripheral T-cell lymphoma–not otherwise specified (n = 13), angioimmunoblastic T-cell lymphoma (n = 9), transformed mycosis fungoides (n = 7), adult T-cell lymphoma/leukemia (n = 4), anaplastic large cell lymphoma (n = 2), and extranodal natural killer/T-cell lymphoma (n = 2). Patients had a median age of 62 years and had received a median of three prior regimens, 65% were male, and 54% were refractory to their last regimen.
Response Rate
Response was observed in 30% of patients with peripheral T-cell lymphoma (complete response in 7%), with a median duration of response of 3 months (range 1–18 months). No responses were observed in patients with transformed mycosis fungoides. Aurora B kinase was more commonly overexpressed than aurora A kinase in tumor specimens. Analysis of aurora A kinase, aurora B kinase, MYC, BCL-2, phosphatidylinositol 3-kinase γ, and Notch1 expression showed no association with response.
Adverse Events
The most common treatment-related adverse events of any grade were anemia (59%), thrombocytopenia (46%), fatigue (46%), and neutropenia (43%). The most common treatment-related grade 3 or 4 adverse events were neutropenia (32%), anemia (30%), and thrombocytopenia (24%); others included febrile neutropenia (14%), mucositis (11%), and rash (5%).
The investigators concluded: “Alisertib has antitumor activity in [peripheral T-cell lymphoma], including heavily pretreated patients. These promising results are being further investigated in an ongoing international, randomized phase III trial comparing alisertib with investigator’s choice in [peripheral T-cell lymphoma].”
Paul M. Barr, MD, of the University of Rochester, is the corresponding author of the Journal of Clinical Oncology article.
The study was supported by National Institutes of Health/National Cancer Institute Cooperative Group grants and National Clinical Trials Network grants. For full disclosures of the study authors, visit jco.ascopubs.org.
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