Principal results of the cancer of the ovary abiraterone trial (CORAL): A phase II study of abiraterone in patients with recurrent epithelial ovarian cancer (CRUKE/12/052)

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.