前列腺癌患者中地加瑞克与亮丙瑞林的心血管安全性：PRONOUNCE 随机试验的主要结果。
Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial.
机构信息
Department of Medicine, Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (R.D.L., A.J.N., C.M., L.A., M.T.R., J.H.A.).
Division of Medical Oncology, University of Washington and Fred Hutchinson Cancer Research Center, Seattle (C.S.H.).
出版信息
Circulation. 2021 Oct 19;144(16):1295-1307. doi: 10.1161/CIRCULATIONAHA.121.056810. Epub 2021 Aug 30.
BACKGROUND
The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial.
METHODS
In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months.
RESULTS
Because of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59-2.79]; =0.53).
CONCLUSIONS
PRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02663908.
背景
与 GnRH 激动剂相比，促性腺激素释放激素（GnRH）拮抗剂在患有前列腺癌和已知动脉粥样硬化性心血管疾病的男性中的相对心血管安全性仍存在争议。
方法
在这项国际性、多中心、前瞻性、随机、开放标签试验中，患有前列腺癌和伴发动脉粥样硬化性心血管疾病的男性被随机 1:1 分配接受 GnRH 拮抗剂地加瑞克或 GnRH 激动剂亮丙瑞林治疗 12 个月。主要结局是通过 12 个月首次判定的主要不良心血管事件（死亡、心肌梗死或中风的复合事件）时间。
结果
由于入组速度慢于预期且主要结局事件少于预期，在计划入组的 900 名患者完成之前，入组提前停止。从 2016 年 5 月 3 日至 2020 年 4 月 16 日，来自 12 个国家 113 个中心的共 545 名患者被随机选择。研究组之间的基线特征平衡。中位年龄为 73 岁，49.8%为局限性前列腺癌；26.3%为局部进展期疾病，20.4%为转移性疾病。15 名（5.5%）接受地加瑞克治疗的患者和 11 名（4.1%）接受亮丙瑞林治疗的患者发生了主要不良心血管事件（风险比，1.28[95%CI，0.59-2.79]；=0.53）。
结论
PRONOUNCE（比较地加瑞克与亮丙瑞林治疗伴有心血管疾病的晚期前列腺癌患者的心血管安全性的一项试验）是第一项国际随机临床试验，前瞻性比较了 GnRH 拮抗剂和 GnRH 激动剂在前列腺癌患者中的心血管安全性。由于参与者和事件数量少于计划，研究提前终止，接受地加瑞克或亮丙瑞林治疗的患者在 1 年时主要不良心血管事件无差异。GnRH 拮抗剂和激动剂的相对心血管安全性仍未解决。注册：网址：https://www.clinicaltrials.gov；唯一标识符：NCT02663908。
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