| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3946898 | Gynecologic Oncology | 2012 | 7 Pages |
ObjectivesAurora 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.MethodsAdult 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.ResultsThirty-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.ConclusionsThese 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.
► 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.
