Phase II study of MLN8237 (Alisertib) in advanced/metastatic sarcoma

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Aurora kinase A (AURKA) is frequently overexpressed in sarcoma.
• AURKA inhibition blocks sarcoma cell proliferation in vitro.
• Alisertib (MLN8237) is an oral AURKA inhibitor.

Purpose of the Study:

• To evaluate the efficacy and safety of alisertib in patients with various sarcoma subtypes.
• To determine the response rate and progression-free survival (PFS) of alisertib treatment.

Main Methods:

• A phase II study (A091102) enrolled patients into histology-defined sarcoma cohorts.
• Patients received alisertib 50 mg twice daily for 7 days every 21 days.
• The primary endpoint was response rate; PFS was secondary, using a Simon two-stage design.

Main Results:

• 72 patients with liposarcoma, leiomyosarcoma, undifferentiated sarcoma, MPNST, or other sarcomas were enrolled.
• Two confirmed partial responses (PRs) in the 'other' cohort (angiosarcoma) and one unconfirmed PR were observed.
• 12-week PFS rates varied by histology, with liposarcoma showing 73% and other subtypes ranging from 36% to 60%.

Conclusions:

• Alisertib was generally well-tolerated in sarcoma patients.
• The study observed occasional responses and prolonged stable disease.
• Despite not meeting the primary response rate endpoint, alisertib demonstrated promising PFS.