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

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

Publication year: 2012
Source:Gynecologic Oncology, Volume 127, Issue 1
Ursula A. Matulonis, Sudarshan Sharma, Sharad Ghamande, Michael S. Gordon, Salvatore A. Del Prete, Isabelle Ray-Coquard, Elzbieta Kutarska, Hua Liu, Howard Fingert, Xiaofei Zhou, Hadi Danaee, Russell J. Schilder
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 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 6.9–11.1month 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.

Highlights

► Aurora A kinase may have a role in the pathobiology of ovarian cancer. ► Investigational agent MLN8237 (alisertib) is an oral Aurora A kinase inhibitor. ► MLN8237 has modest antitumor activity in platinum-resistant ovarian cancer.

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