title: 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.
abstract: OBJECTIVE
  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.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Ursula_Matulonis@dfci.harvard.edu
authors: Ursula A
authors: UA
authors: Matulonis
authors: Sudarshan
authors: S
authors: Sharma
authors: Sharad
authors: S
authors: Ghamande
authors: Michael S
authors: MS
authors: Gordon
authors: Salvatore A
authors: SA
authors: Del Prete
authors: Isabelle
authors: I
authors: Ray-Coquard
authors: Elzbieta
authors: E
authors: Kutarska
authors: Hua
authors: H
authors: Liu
authors: Howard
authors: H
authors: Fingert
authors: Xiaofei
authors: X
authors: Zhou
authors: Hadi
authors: H
authors: Danaee
authors: Russell J
authors: RJ
authors: Schilder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064127:Aurora Kinases; D001381:Azepines / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001381:Azepines; C550258:MLN 8237; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases