AURORA KINASE INHIBITORS

Gynecol Oncol. 2012 Jul 5. [Epub ahead of print]

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 UA, Sharma S, Ghamande S, Gordon MS, Del Prete SA, Ray-Coquard I, Kutarska E, Liu H, Fingert H, Zhou X, Danaee H, Schilder RJ.

Source

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Abstract

BACKGROUND:

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 7days plus 14days' 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 6.9-11.1months 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 2.86months and which was durable for ≥3months in 6 (19%). Median PFS and TTP were 1.9months. 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.