Banerjee Susana, Tovey Holly, Bowen Rebecca, Folkerd Elizabeth, Kilburn Lucy, McLachlan Jennifer, Hall Marcia, Tunariu Nina, Attygalle Ayoma, Lima Joao Paulo Da Silveira Nogueira, Perry Sophie, Chatfield Peter, Hills Margaret, Kaye Stan, Attard Gert, Dowsett Mitch, Bliss Judith M
Gynaecology Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, SM2 5PT, UK.
Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK.
Ther Adv Med Oncol. 2020 Dec 29;12:1758835920975352. doi: 10.1177/1758835920975352. eCollection 2020.
Recurrent epithelial ovarian cancer (EOC) remains difficult to treat, with an urgent need for more therapy options. Androgens bind to the androgen receptor (AR), commonly expressed in EOC. CYP17 inhibitor abiraterone irreversibly inhibits androgen biosynthesis. The Cancer of the Ovary Abiraterone (CORAL) trial was designed to evaluate the clinical activity of abiraterone in EOC.
PATIENTS & METHODS: CORAL was a multi-centre, open-label, non-randomised, 2-stage phase II clinical trial. Eligible patients had progression within 12 months of last systemic therapy and no prior hormonal anti-cancer agents. Patients received abiraterone 1000 mg daily plus 5 mg prednisone until progression. The primary endpoint was objective response rate (ORR) according to combined Response Evaluation Criteria in Solid Tumours/Gynaecological Cancer Intergroup (RECIST/GCIG) criteria at 12 weeks. Secondary endpoints included clinical benefit rate (CBR) at 12 weeks.
A total of 42 patients were recruited; median age 65 (range 34-85) years; 37 (88.1%) had high-grade serous tumours; 20 (48%) had at least three prior lines of therapy; 29/40 (72.5%) were AR+. In stage 1, 1/26 response was observed (in an AR+, low-grade serous EOC); response lasted 47 weeks. Overall, 12 week ORR was 1/42 (2%), CBR was 11/42 (26%) (8/29 (28%) in AR+ patients). Disease control was ⩾6 months for 4/29 (14%). One patient (AR+, low-grade serous) had a RECIST response at 82 weeks. Four (10%) had grade ⩾3 hypokalaemia; 11 (26%) had dose delays.
CORAL represents the first trial of an AR targeted agent in ovarian cancer. While responses were rare, a subset of patients achieved sustained clinical benefit. Targeting AR in EOC including low-grade serous cancer warrants further investigation.
CORAL is registered on the ISRCTN registry: ISRCTN63407050; http://www.isrctn.com/ISRCTN63407050.
复发性上皮性卵巢癌（EOC）的治疗仍然困难，迫切需要更多的治疗选择。雄激素与EOC中普遍表达的雄激素受体（AR）结合。CYP17抑制剂阿比特龙不可逆地抑制雄激素生物合成。卵巢癌阿比特龙（CORAL）试验旨在评估阿比特龙在EOC中的临床活性。
CORAL是一项多中心、开放标签、非随机的2期II期临床试验。符合条件的患者在最后一次全身治疗的12个月内病情进展，且之前未使用过激素抗癌药物。患者接受每日1000mg阿比特龙加5mg泼尼松治疗，直至病情进展。主要终点是根据实体瘤/妇科癌症协作组（RECIST/GCIG）联合标准在12周时的客观缓解率（ORR）。次要终点包括12周时的临床获益率（CBR）。
共招募了42例患者；中位年龄65岁（范围34 - 85岁）；37例（88.1%）患有高级别浆液性肿瘤；20例（48%）至少接受过三线先前治疗；29/40例（72.5%）为AR阳性。在第1阶段，观察到1例缓解（在1例AR阳性、低级别浆液性EOC患者中）；缓解持续了47周。总体而言，12周时的ORR为1/42（2%），CBR为11/42（26%）（AR阳性患者中为8/29（28%））。4/29例（14%）患者的疾病控制时间≥6个月。1例患者（AR阳性、低级别浆液性）在82周时出现RECIST缓解。4例（10%）患者发生≥3级低钾血症；11例（26%）患者出现剂量延迟。
CORAL是卵巢癌中首个针对AR的药物试验。虽然缓解罕见，但一部分患者获得了持续的临床获益。在包括低级别浆液性癌在内的EOC中靶向AR值得进一步研究。
CORAL在ISRCTN注册中心注册：ISRCTN63407050；http://www.isrctn.com/ISRCTN63407050 。
