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

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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

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Aurora Kinase A
Fallopian Tubes
Platinum
Ovarian Neoplasms
Carcinoma
Disease-Free Survival
Safety
Febrile Neutropenia
Stomatitis
Leukopenia
Paclitaxel
Neutropenia
Thrombocytopenia
Antineoplastic Agents
Neoplasms
MLN 8237
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

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

In: Gynecologic Oncology, Vol. 127, No. 1, 01.10.2012, p. 63-69.

Research output: Contribution to journalArticle

Matulonis, Ursula A. ; Sharma, Sudarshan ; Ghamande, Sharad A ; Gordon, Michael S. ; Del Prete, Salvatore A. ; Ray-Coquard, Isabelle ; Kutarska, Elzbieta ; Liu, Hua ; Fingert, Howard ; Zhou, Xiaofei ; Danaee, Hadi ; Schilder, Russell J. / 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. In: Gynecologic Oncology. 2012 ; Vol. 127, No. 1. pp. 63-69.
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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.",
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AU - Sharma, Sudarshan

AU - Ghamande, Sharad A

AU - Gordon, Michael S.

AU - Del Prete, Salvatore A.

AU - Ray-Coquard, Isabelle

AU - Kutarska, Elzbieta

AU - Liu, Hua

AU - Fingert, Howard

AU - Zhou, Xiaofei

AU - Danaee, Hadi

AU - Schilder, Russell J.

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