Alisertib yielded promising progression-free survival in advanced/metastatic soft-tissue sarcoma patients, though it did not meet its primary response rate endpoint.
A phase II trial of the novel agent alisertib found that the drug was well tolerated and yielded promising progression-free survival (PFS) in advanced/metastatic soft-tissue sarcoma (STS) patients, though it did not meet its primary response rate endpoint.
Alisertib is an inhibitor of aurora kinase A (AURKA). “AURKA is commonly overexpressed in STS and inhibition of AURKA by shRNA or by a specific AURKA inhibitor inhibits proliferation of STS cells,” wrote study authors led by Mark A. Dickson, MD, of Memorial Sloan Kettering Cancer Center in New York.
This trial included 5 cohorts totaling 72 patients: 12 with liposarcoma, 10 with leiomyosarcoma, 11 with undifferentiated sarcoma, 10 with malignant peripheral nerve sheath tumor (MPNST), and 29 categorized as “other” types of sarcoma. Patients received alisertib 50 mg twice daily for days 1 to 7 every 21 days, and response rate was the primary endpoint. The results were published in Annals of Oncology.
In total, there were two confirmed partial responses in the “other” cohort; both of these patients had angiosarcoma, and stayed on treatment for 4.6 and 7 months. There were no other confirmed responses, yielding a response rate of 2.8%.
The median PFS was 11.7 weeks in the full study. The PFS rates were 13 weeks for liposarcoma, 11.7 weeks for leiomyosarcoma, 11.7 weeks for undifferentiated sarcoma, 13 weeks for MPNST, and 6.6 weeks in the other types of sarcoma. PFS rates at 12 weeks were 73%, 44%, 36%, 60%, and 38%, respectively.
The median overall survival was 68 weeks for liposarcoma, 72 weeks for leiomyosarcoma, 68 weeks for undifferentiated sarcoma, 69 weeks for MPNST, and 29 weeks for other sarcomas. The authors noted that several patients did maintain stable disease for prolonged periods, including one with undifferentiated sarcoma and three patients in the “other”cohort with alveolar soft part sarcoma, chondrosarcoma, and Ewing sarcoma.
Among the more common grade 3/4 toxicities were decreased neutrophil count (42% of all patients), decreased white blood cells (22%), anemia (14%), and others. The authors wrote that the myelosuppressive adverse events were expected and were generally manageable.
“Further study of aurora kinase inhibitors in angiosarcoma would be warranted, especially since angiosarcoma is known to be sensitive to mitotic inhibitors such as taxanes,” the authors wrote. They noted that some sarcoma experts now advocate using PFS as the primary endpoint in clinical trials. “By this metric, the results of alisertib are promising, especially in liposarcoma,” they wrote.