Phase II study of MLN8237 (alisertib), an investigational Aurora A kinase inhibitor, in patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal carcinoma

Gynecol Oncol. 2012 Oct;127(1):63-9. doi: 10.1016/j.ygyno.2012.06.040. Epub 2012 Jul 5.


Objectives: Aurora A kinase (AAK), a key mitotic regulator, is implicated in the pathogenesis of several tumors, including ovarian cancer. This single-arm phase II study assessed single-agent efficacy and safety of the investigational AAK inhibitor MLN8237 (alisertib), in patients with platinum-refractory or -resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.

Methods: Adult women with malignant, platinum-treated disease received MLN8237 50mg orally twice daily for 7 days plus 14 days' rest (21-day cycles). The primary endpoint was combined objective tumor response rate per Response Evaluation Criteria in Solid Tumors (RECIST) and/or CA-125 criteria. Secondary endpoints included response duration, clinical benefit rate, progression-free survival (PFS), time-to-progression (TTP), and safety.

Results: Thirty-one patients with epithelial ovarian (n=25), primary peritoneal (n=5), and fallopian tube carcinomas (n=1) were enrolled. Responses of 6.9-11.1 month duration were observed in 3 (10%) patients with platinum-resistant ovarian cancer. Sixteen (52%) patients achieved stable disease with a mean duration of response of 2.86 months and which was durable for ≥3 months in 6 (19%). Median PFS and TTP were 1.9 months. Most common drug-related grade≥3 adverse events were neutropenia (42%), leukopenia (23%), stomatitis, and thrombocytopenia (each 19%); 6% reported febrile neutropenia.

Conclusions: These data suggest that MLN8237 has modest single-agent antitumor activity and may produce responses and durable disease control in some patients with platinum-resistant ovarian cancer. MLN8237 is currently undergoing evaluation in a phase I/II trial with paclitaxel in recurrent ovarian cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aurora Kinases
  • Azepines / adverse effects
  • Azepines / therapeutic use*
  • Disease-Free Survival
  • Fallopian Tube Neoplasms / drug therapy*
  • Fallopian Tube Neoplasms / enzymology
  • Fallopian Tube Neoplasms / pathology
  • Female
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / pathology
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / enzymology
  • Peritoneal Neoplasms / pathology
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*


  • Azepines
  • MLN 8237
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases