Bonaventura Anthony, OʼConnell Rachel L, Mapagu Cristina, Beale Philip J, McNally Orla M, Mileshkin Linda R, Grant Peter T, Hadley Alison M, Goh Jeffery C H, Sjoquist Katrin M, Martyn Julie, DeFazio Anna, Scurry James, Friedlander Michael L
*Calvary Mater Newcastle, Newcastle; †National Health and Medical Research Council Clinical Trials Centre and ‡Westmead Institute for Medical Research, University of Sydney, Sydney; §Department of Gynaecological Oncology, Westmead Hospital, Westmead; and ∥School of Medicine, Western Sydney University; ¶Chris O'Brien Lifehouse; and #School of Medicine, University of Sydney, Sydney, New South Wales; **Royal Women's Hospital; ††University of Melbourne; ‡‡Division of Cancer Medicine, Peter MacCallum Cancer Centre; and §§Mercy Hospital for Women, Melbourne, Victoria; ∥∥Royal Brisbane and Women's Hospital and ¶¶School of Medicine, University of Queensland, Brisbane, Queensland; and ##Pathology North and ***Faculty of Health and Medicine, University of Newcastle, Newcastle; and †††Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
Int J Gynecol Cancer. 2017 Jun;27(5):900-906. doi: 10.1097/IGC.0000000000000978.
There is some evidence that a subset of patients with recurrent ovarian cancer may benefit from antiestrogen therapy. The Paragon study is a basket protocol that includes a series of phase 2 trials investigating the activity of anastrozole in patients with estrogen or progesterone receptor-positive recurrent gynecological cancers. We report the results of treatment in patients with platinum-resistant or -refractory recurrent epithelial ovarian cancer.
Postmenopausal women who had estrogen and/or progesterone receptor-positive platinum-resistant or platinum-refractory recurrent ovarian cancer and disease measurable by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or GCIG (Gynecologic Cancer InterGroup) CA-125 criteria were eligible. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity. The study was prospectively registered (ACTRN12610000796088).
There were 49 evaluable patients, and clinical benefit was observed in 13 (27%; 95% confidence interval [CI], 16%-40%). There were no complete or partial RECIST version 1.1 responses. Clinical benefit was associated with higher global quality-of-life scores. Median progression-free survival was 2.7 months (95% CI, 2.0-2.8 months). The median duration of clinical benefit was 2.8 months (95% CI, 2.6-5.7 months). Most patients (83%) progressed within 6 months. Seven patients continued on treatment for longer than 6 months. Anastrozole was well tolerated in most patients. Subgroup analysis suggested greater clinical benefit in patients with tumors with estrogen-receptor histoscore of more than 200, but this difference was not statistically significant.
A subset of patients with estrogen- or progesterone-positive platinum-resistant or platinum-refractory recurrent epithelial ovarian cancers derives clinical benefit from anastrozole, with acceptable toxicity. The challenge remains how to identify them.
有证据表明，一部分复发性卵巢癌患者可能从抗雌激素治疗中获益。帕拉贡研究是一项篮子试验方案，包括一系列2期试验，旨在研究阿那曲唑在雌激素或孕激素受体阳性的复发性妇科癌症患者中的活性。我们报告了铂耐药或难治性复发性上皮性卵巢癌患者的治疗结果。
符合条件的患者为绝经后女性，患有雌激素和/或孕激素受体阳性的铂耐药或铂难治性复发性卵巢癌，且疾病可通过实体瘤疗效评价标准（RECIST）1.1版或妇科癌症国际协作组（GCIG）CA-125标准进行测量。患者每天接受1 mg阿那曲唑治疗，直至病情进展或出现不可接受的毒性反应。该研究已进行前瞻性注册（ACTRN12610000796088）。
有49例可评估患者，其中13例（27%；95%置信区间[CI]，16%-40%）观察到临床获益。未观察到RECIST 1.1版的完全或部分缓解。临床获益与更高的总体生活质量评分相关。中位无进展生存期为2.7个月（95% CI，2.0-2.8个月）。临床获益的中位持续时间为2.8个月（95% CI，2.6-5.7个月）。大多数患者（83%）在6个月内病情进展。7例患者继续治疗超过6个月。大多数患者对阿那曲唑耐受性良好。亚组分析表明，雌激素受体组织评分大于200的肿瘤患者临床获益更大，但这种差异无统计学意义。
一部分雌激素或孕激素阳性、铂耐药或铂难治性复发性上皮性卵巢癌患者可从阿那曲唑治疗中获得临床获益，且毒性可接受。如何识别这些患者仍是一个挑战。
