口服Relugolix治療晚期前列腺癌雄激素剝奪療效顯著
作者：
小柯機器人發布時間：2020/6/1 19:31:13
美國卡羅萊納泌尿外科研究中心Neal D. Shore團隊近日探討了口服Relugolix在晚期前列腺癌雄激素剝奪中的療效。2020年5月29日出版的《新英格蘭醫學雜誌》發表了該成果。
注射性促黃體生成素釋放激素激動劑（如亮丙瑞林）是前列腺癌雄激素剝奪的標準藥物，儘管最初睪酮激增和治療效果延遲。與亮丙瑞林相比，一種口服促性腺激素釋放激素拮抗劑relugolix的療效和安全性尚不清楚。
在這項臨床3期試驗中，研究組按2：1隨機分配晚期前列腺癌患者，其中622例接受Relugolix治療，308例接受亮丙瑞林治療，持續48周。主要終點是48周將睪酮持續抑制至去勢水平（<50 ng/dL）。
Relugolix組中有96.7％的患者維持去勢48周，而亮丙瑞林組為88.8％。7.9個百分點的差異顯示了Relugolix的非劣效性和優越性。Relugolix組的所有其他關鍵指標均優於亮丙瑞林組。治療第4天，Relugolix組中有56.0%的患者睪酮降至去勢水平，亮丙瑞林組中為0%。在對睪酮恢復的184名患者的亞組進行隨訪時，停藥後90天，Relugolix組的平均睪酮水平為288.4 ng/dL，亮丙瑞林組為58.6 ng/dL。在所有患者中，Relugolix組的主要不良心血管事件發生率為2.9％，而亮丙瑞林組為6.2％，風險比為0.46。
總之，對於晚期前列腺癌男性，Relugolix實現了對睪酮水平的快速、持續抑制，其效果優於亮丙瑞林，且主要不良心血管事件的風險降低了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