학술논문
Phase II study of enzalutamide in androgen receptor positive, recurrent, high- and low-grade serous ovarian cancer.
Document Type
Article
Author
Manning-Geist, Beryl L.; Gordhandas, Sushmita B.; Giri, Dilip D.; Iasonos, Alexia; Zhou, Qin; Girshman, Jeffrey; O'Cearbhaill, Roisin E.; Zamarin, Dmitriy; Lichtman, Stuart M.; Sabbatini, Paul J.; Tew, William P.; Li, Karen; McDonnell, Autumn S.; Aviki, Emeline M.; Chi, Dennis S.; Aghajanian, Carol A.; Grisham, Rachel N.
Source
Subject
*ANDROGEN receptors
*OVARIAN cancer
*TERMINATION of treatment
*INFORMED consent (Medical law)
*ANTIANDROGENS
*PROGRESSION-free survival
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Language
ISSN
0090-8258
Abstract
We sought to determine the safety and efficacy of the oral androgen receptor antagonist enzalutamide in patients with previously treated, recurrent, AR-positive (AR+) ovarian cancer. This was a single-institution phase II study of patients with AR+ ovarian cancer with measurable disease with 1–3 prior lines of chemotherapy; patients were screened for enrollment from 11/2013–7/2018. Following consent, archival tissue was evaluated for AR+. Enrolled patients received daily enzalutamide 160 mg until progression of disease or treatment discontinuation. Adverse events were graded by CTCAE v4.0. Co-primary endpoints were 6-month progression-free survival (PFS 6) and overall response rate (ORR) by RECIST 1.1 criteria. During the study period, 160 patients were screened and 59 (45 high-grade serous [HGS] and 14 low-grade serous [LGS]) consented to treatment on study. There was 1 confirmed and 1 unconfirmed partial response. The ORR was 1.7% (90% CI: 0.2–100%). The overall PFS 6 rate (as binary) was 22% (90% CI: 15.1–100%). The 6-month PFS rate (as time to event) was 19.8% for HGS patients (90% CI: 12.7–100%) and 38.5% (90% CI: 21.7%–100%) for LGS patients. Grade 3 toxicities occurred in 6 patients (one toxicity (Grade 3 rash) was considered a dose-limiting toxicity). One patient died of cardiac arrest after 42 days on treatment of a cardiac arrest not attributed to study drug. The study met its primary endpoint, with a PFS 6 rate of 22% (n = 13); however, the overall response rate was low. Enzalutamide was well tolerated and may be a potential treatment option in select patients. • Enzalutamide was well-tolerated in AR+ recurrent ovarian cancer patients and demonstrated a suitable safety profile. • This study met its primary endpoint, as enzalutamide afforded modest progression-free survival. • The overall response rate to enzalutamide was low, with less than 2% of patients demonstrating radiographic response. • Further study of enzalutamide may be warranted, particularly in patients with AR+ low-grade serous ovarian cancer. [ABSTRACT FROM AUTHOR]