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

Ursula A. Matulonis, Sudarshan Sharma, Sharad A Ghamande, Michael S. Gordon, Salvatore A. Del Prete, Isabelle Ray-Coquard, Elzbieta Kutarska, Hua Liu, Howard Fingert, Xiaofei Zhou, Hadi Danaee, Russell J. Schilder

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

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 50 mg 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.

Original languageEnglish (US)
Pages (from-to)63-69
Number of pages7
JournalGynecologic Oncology
Volume127
Issue number1
DOIs
StatePublished - Oct 1 2012

Keywords

  • Aurora A kinase
  • MLN8237
  • Ovarian cancer
  • Platinum-refractory
  • Platinum-resistant

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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