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

Mark A. Dickson*, M. R. Mahoney, W. D. Tap, S. P. D'Angelo, M. L. Keohan, B. A. Van Tine, M. Agulnik, L. E. Horvath, J. S. Nair, G. K. Schwartz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Background: Aurora kinase A (AURKA) is commonly overexpressed in sarcoma. The 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 adenosine triphosphate-competitive AURKA inhibitor. Patients and methods: This Cancer Therapy Evaluation Program-sponsored phase II study of alisertib was conducted through the Alliance for Clinical Trials in Oncology (A091102). Patients were enrolled into histology-defined cohorts: (i) liposarcoma, (ii) leiomyosarcoma, (iii) undifferentiated sarcoma, (iv) malignant peripheral nerve sheath tumor, or (v) other. Treatment was alisertib 50 mg PO b.i.d. d1-d7 every 21 days. The primary end point was response rate; progression-free survival (PFS) was secondary. One response in the first 9 patients expanded enrollment in a cohort to 24 using a Simon two-stage design. Results: Seventy-two patients were enrolled at 24 sites [12 LPS, 10 LMS, 11 US, 10 malignant peripheral nerve sheath tumor (MPNST), 29 Other]. The median age was 55 years; 54% were male; 58%/38%/4% were ECOG PS 0/1/2. One PR expanded enrollment to the second stage in the other sarcoma cohort. The histology-specific cohorts ceased at the first stage. There were two confirmed PRs in the other cohort (both angiosarcoma) and one unconfirmed PR in dedifferentiated chondrosarcoma. Twelve-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 end point, PFS was promising. Trial registration ID: NCT01653028.

Original languageEnglish (US)
Pages (from-to)1855-1860
Number of pages6
JournalAnnals of Oncology
Issue number10
StatePublished - 2016


  • Aurora kinase inhibitors
  • Bone sarcoma
  • Phase II clinical trials
  • Soft tissue sarcoma

ASJC Scopus subject areas

  • Hematology
  • Oncology


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