National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
Chris O'Brien Lifehouse, Sydney, NSW, Australia.
J Gynecol Oncol. 2019 Sep;30(5):e86. doi: 10.3802/jgo.2019.30.e86.
A subset of patients with recurrent ovarian cancer (ROC) may benefit from antiestrogen therapy with higher response rates reported in tumors that are strongly estrogen receptor (ER)-positive (ER⁺). PARAGON is a basket trial that incorporates 7 phase 2 trials investigating the activity of anastrozole in patients with ER⁺ and/or progesterone receptor (PR)-positive (PR⁺) recurrent/metastatic gynecological cancers.
Postmenopausal women with ER⁺ and/or PR⁺ ROC, who were asymptomatic and had cancer antigen 125 (CA125) progression after response to first line chemotherapy, where chemotherapy was not clinically indicated. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity.
Fifty-four patients were enrolled (52 evaluable). Clinical benefit at three months (primary endpoint) was observed in 18 patients (34.6%; 95% confidence interval [CI]=23%-48%). Median progression-free survival (PFS) was 2.7 months (95% CI=2.1-3.1). The median duration of clinical benefit was 6.5 months (95% CI=2.8-11.7). Most patients progressed within 6 months of starting anastrozole but 12 (22%) continued treatment for longer than 6 months. Anastrozole was well tolerated. In the exploratory analysis, ER histoscores and the intensity of ER staining did not correlate with clinical benefit rate or PFS.
A subset of asymptomatic patients with ER⁺ and/or PR⁺ ROC and CA125 progression had durable clinical benefit on anastrozole, with acceptable toxicity. Anastrozole may delay symptomatic progression and the time to subsequent chemotherapy. The future challenge is to identify the subset of patients most likely to benefit from an aromatase inhibitor and whether the clinical benefit could be increased by the addition of other agents.
一些复发性卵巢癌（ROC）患者可能受益于抗雌激素治疗，报告称肿瘤雌激素受体（ER）阳性（ER⁺）的患者有更高的反应率。PARAGON 是一项纳入了 7 项 2 期临床试验的篮子试验，研究了阿那曲唑在 ER⁺和/或孕激素受体（PR）阳性（PR⁺）复发性/转移性妇科癌症患者中的活性。
入组患者为绝经后 ER⁺和/或 PR⁺ROC 患者，在一线化疗缓解后无症状且癌症抗原 125（CA125）进展，且化疗不具有临床指征。患者接受阿那曲唑 1 mg 每日一次治疗，直至疾病进展或出现不可耐受的毒性。
共纳入 54 例患者（52 例可评估）。在三个月时观察到临床获益（主要终点）的患者有 18 例（34.6%；95%置信区间 [CI]=23%-48%）。中位无进展生存期（PFS）为 2.7 个月（95%CI=2.1-3.1）。中位临床获益持续时间为 6.5 个月（95%CI=2.8-11.7）。大多数患者在开始使用阿那曲唑后 6 个月内进展，但有 12 例（22%）患者继续治疗超过 6 个月。阿那曲唑耐受良好。在探索性分析中，ER 组织学评分和 ER 染色强度与临床获益率或 PFS 均无相关性。
在 ER⁺和/或 PR⁺ROC 且 CA125 进展的无症状患者亚组中，阿那曲唑具有持久的临床获益，且毒性可接受。阿那曲唑可能延迟症状性进展和后续化疗的时间。未来的挑战是确定最有可能从芳香化酶抑制剂中获益的患者亚组，以及添加其他药物是否能增加临床获益。
