Phase II Study of MLN8237 (Alisertib) in Advanced/Metastatic Sarcoma.

Phase II Study of MLN8237 (Alisertib) in Advanced/Metastatic Sarcoma.

Ann Oncol. 2016 Aug 8;

Authors: Dickson MA, Mahoney MR, Tap WD, D'Angelo SP, Keohan ML, Van Tine BA, Agulnik M, Horvath LE, Nair JS, Schwartz GK

Abstract
BACKGROUND: Aurora Kinase A (AURKA) is commonly overexpressed in sarcoma. Inhibition of AURKA by shRNA or by a specific AURKA inhibitor blocks in vitro proliferation of multiple sarcoma subtypes. MLN8237 (alisertib) is a novel oral ATP-competitive AURKA inhibitor.
PATIENTS AND METHODS: This CTEP-sponsored phase II study of alisertib was conducted through the Alliance for Clinical Trials in Oncology (A091102). Patients were enrolled into histology-defined Cohorts: 1) liposarcoma, 2) leiomyosarcoma, 3) undifferentiated sarcoma, 4) malignant peripheral nerve sheath tumor, or 5) Other. Treatment was alisertib 50 mg PO BID d1-d7 every 21 days. The primary endpoint was response rate; progression-free survival (PFS) was secondary. 1 response in the first 9 patients expanded enrollment in a cohort to 24 using a Simon 2-stage design.
RESULTS: 72 patients were enrolled at 24 sites (12 LPS, 10 LMS, 11 US, 10 MPNST, 29 Other). Median age was 55 yrs; 54% were male; 58/38/4% were ECOG PS 0/1/2. 1 PR expanded enrollment to the 2nd stage in other sarcoma cohort. The histology-specific cohorts ceased at the 1st stage. There were 2 confirmed PRs in other cohort (both angiosarcoma) and 1 unconfirmed PR in dedifferentiated chondrosarcoma. 12-week PFS was 73% (LPS), 44% (LMS), 36% (US), 60% (MPNST), and 38% (Other). Grade 3-4 adverse events: oral mucositis (12%), anemia (14%), platelet count decreased (14%), leukopenia (22%), and neutropenia (42%).
CONCLUSIONS: Alisertib was well-tolerated. Occasional responses, yet prolonged stable disease, were observed. Although failing to meet the primary RR endpoint, PFS was promising.
TRIAL REGISTRATION ID: NCT01653028.

PMID: 27502708 [PubMed - as supplied by publisher]

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