Saad Fred, George Daniel J, Cookson Michael S, Saltzstein Daniel R, Tutrone Ronald, Bossi Alberto, Brown Bruce, Selby Bryan, Lu Sophia, Tombal Bertrand, Shore Neal D
University of Montreal Hospital Centre, Montreal, QC H2X 3E4, Canada.
Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC 27710, USA.
Cancers (Basel). 2023 Oct 5;15(19):4854. doi: 10.3390/cancers15194854.
Relugolix is an oral GnRH receptor antagonist approved for men with advanced prostate cancer. Relugolix treatment has demonstrated an ability to lower testosterone to sustained castration levels in the phase 4 HERO study. Herein, we describe the results of a secondary endpoint of castration resistance-free survival (CRFS) during 48 weeks of treatment and profile patients with castration-resistant prostate cancer (CRPC). Subjects were 2:1 randomized to either relugolix 120 mg orally once daily (after a single 360 mg loading dose) or 3-monthly injections of leuprolide for 48 weeks. CRFS, defined as the time from the date of first dose to the date of confirmed prostate-specific antigen progression while castrated or death due to any reason was conducted in the metastatic disease population and the overall modified intention-to-treat (mITT) populations. The CRFS analysis (mITT population) included 1074 men (relugolix: n = 717; leuprolide: n = 357) with advanced prostate cancer as well as 434 men (relugolix: n = 290; leuprolide: n = 144) with metastatic prostate cancer. In the metastatic disease populations, CRFS rates were 74.3% (95% CI: 68.6%, 79.2%) and 75.3% (95% CI: 66.7%, 81.9%) in the relugolix and leuprolide groups, respectively (hazard ratio: 1.03 [0.68, 1.57]; = 0.84) at week 48. Results in the overall mITT population were similar to the metastatic population. No new safety findings were identified. In men with metastatic disease or in the overall population of the HERO study, CRFS assessed during the 48-week treatment with relugolix was not significantly different than standard-of-care leuprolide. Relugolix had similar efficacy for men with/without CRFS progression events.
relugolix是一种口服促性腺激素释放激素（GnRH）受体拮抗剂，已被批准用于治疗晚期前列腺癌男性患者。在4期HERO研究中，relugolix治疗已显示出将睾酮降低至持续去势水平的能力。在此，我们描述了治疗48周期间去势抵抗无进展生存期（CRFS）这一次要终点的结果，并对去势抵抗性前列腺癌（CRPC）患者进行了分析。受试者按2:1随机分组，分别接受relugolix 120 mg每日一次口服给药（单次360 mg负荷剂量后）或每3个月注射一次亮丙瑞林，共治疗48周。CRFS定义为从首次给药日期到确认前列腺特异性抗原进展日期（处于去势状态时）或因任何原因死亡的时间，在转移性疾病人群和总体改良意向性治疗（mITT）人群中进行评估。CRFS分析（mITT人群）纳入了1074例晚期前列腺癌男性患者（relugolix组：n = 717；亮丙瑞林组：n = 357）以及434例转移性前列腺癌男性患者（relugolix组：n = 290；亮丙瑞林组：n = 144）。在转移性疾病人群中，第48周时relugolix组和亮丙瑞林组的CRFS率分别为74.3%（95%CI：68.6%，79.2%）和75.3%（95%CI：66.7%，81.9%）（风险比：1.03[0.68，1.57]；P = 0.84）。总体mITT人群的结果与转移性人群相似。未发现新的安全性问题。在HERO研究的转移性疾病男性患者或总体人群中，relugolix治疗48周期间评估的CRFS与标准治疗药物亮丙瑞林无显著差异。relugolix对有/无CRFS进展事件的男性患者疗效相似。
