美国卡罗莱纳泌尿外科研究中心Neal D. Shore团队近日探讨了口服Relugolix在晚期前列腺癌雄激素剥夺中的疗效。2020年5月29日出版的《新英格兰医学杂志》发表了该成果。

注射性促黄体生成素释放激素激动剂（如亮丙瑞林）是前列腺癌雄激素剥夺的标准药物，尽管最初睾酮激增和治疗效果延迟。与亮丙瑞林相比，一种口服促性腺激素释放激素拮抗剂relugolix的疗效和安全性尚不清楚。

在这项临床3期试验中，研究组按2：1随机分配晚期前列腺癌患者，其中622例接受Relugolix治疗，308例接受亮丙瑞林治疗，持续48周。主要终点是48周将睾酮持续抑制至去势水平（<50 ng/dL）。

Relugolix组中有96.7％的患者维持去势48周，而亮丙瑞林组为88.8％。7.9个百分点的差异显示了Relugolix的非劣效性和优越性。Relugolix组的所有其他关键指标均优于亮丙瑞林组。治疗第4天，Relugolix组中有56.0%的患者睾酮降至去势水平，亮丙瑞林组中为0%。在对睾酮恢复的184名患者的亚组进行随访时，停药后90天，Relugolix组的平均睾酮水平为288.4 ng/dL，亮丙瑞林组为58.6 ng/dL。在所有患者中，Relugolix组的主要不良心血管事件发生率为2.9％，而亮丙瑞林组为6.2％，风险比为0.46。

总之，对于晚期前列腺癌男性，Relugolix实现了对睾酮水平的快速、持续抑制，其效果优于亮丙瑞林，且主要不良心血管事件的风险降低了54％。

附：英文原文

Title: Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer | NEJM

Author: Neal D. Shore, M.D.,, Fred Saad, M.D.,, Michael S. Cookson, M.D., M.M.H.C.,, Daniel J. George, M.D.,, Daniel R. Saltzstein, M.D.,, Ronald Tutrone, M.D.,, Hideyuki Akaza, M.D.,, Alberto Bossi, M.D.,, David F. van Veenhuyzen, M.B., Ch.B., M.Pharm.Med.,, Bryan Selby, M.S.,, Xiaolin Fan, Ph.D.,, Vicky Kang, M.D.,, Jackie Walling, M.B., Ch.B., Ph.D.,, and Bertrand Tombal, M.D., Ph.D.

Issue&Volume: 2020-05-29

Abstract: Abstract

Background

Injectable luteinizing hormone–releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known.

Methods

In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients.

Results

A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88).

Conclusions

In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events.

DOI: 10.1056/NEJMoa2004325

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2004325