There is a need for more therapy options in recurrent epithelial ovarian cancer (EOC). Androgens bind to the androgen receptor (AR) which is commonly expressed in EOC. Abiraterone, a CYP17 inhibitor, irreversibly inhibits androgen biosynthesis and is widely used in prostate cancer. CORAL was designed to evaluate the clinical activity of abiraterone in EOC.
CORAL is a prospective, multi-centre, open-label, non-randomised, 2-stage phase II clinical trial. Eligible patients had disease progression within 12 months of last systemic therapy and no prior hormonal anti-cancer agents. Patients received abiraterone 1000mg daily plus 5 mg prednisone continuously until disease progression. The primary endpoint is objective response rate (ORR) according to combined RECIST/GCIG criteria at 12 weeks. Secondary endpoints include clinical benefit rate (CBR = ORR + stable) at 12 weeks. Tissue and blood samples were collected to explore the AR signalling pathway in EOC and identify patients most likely to benefit from abiraterone.
42 patients were recruited (median age 65 (range 34-85) years; 83% high grade serous; median time since initial diagnosis 2.8 years (IQR 2-5) and 47% had ≥3 prior lines of therapy). Using a 10% cut-off, 29 (69%) patients were AR+. 10% had ≥ grade 3 hypokalaemia; 24% had dose delays and 0% dose reductions. ORR was 1/42 (2%). This 1 response was in an AR + , low grade serous EOC patient and lasted 47 weeks. CBR was 11/42 (26%) and 8/29 (28%) in AR+ patients; in 4 of these 29 (14%), disease control was prolonged ≥ 6 months. 1 patient continues on abiraterone.
CORAL is the first trial of a CYP17 inhibitor targeting the AR pathway in ovarian cancer patients. While ORR was low, a subset of patients achieved sustained clinical benefit and detailed characterisation of these patients is underway. Targeting AR in EOC including low grade serous cancer warrants further investigation.
Clinical trial identification
EudraCT Number: 2013-000293-29 (17-01-2013)
Legal entity responsible for the study
The Institute of Cancer Research/The Royal Marsden Hospital NHS Foundation Trust
Janssen Cilag Ltd
G. Attard: On the ICR "rewards to inventors" list for abiraterone acetate. Has received consulting fees and travel support from Janssen-Cilag and speakers' fees and grant support from Janssen. M. Dowsett: On the ICR "rewards to inventors" list for abiraterone acetate. All other authors have declared no conflicts of interest.