TY - JOUR
T1 - 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
AU - Matulonis, Ursula A.
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.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Aurora A kinase
KW - MLN8237
KW - Ovarian cancer
KW - Platinum-refractory
KW - Platinum-resistant
UR - http://www.scopus.com/inward/record.url?scp=84865681647&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865681647&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2012.06.040
DO - 10.1016/j.ygyno.2012.06.040
M3 - Article
C2 - 22772063
AN - SCOPUS:84865681647
SN - 0090-8258
VL - 127
SP - 63
EP - 69
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 1
ER -