De La Cerda Jose, Belkoff Laurence, Courtney Kevin D, Diamond Elan, D'Olimpio James, Dunshee Curtis, Gervasi Lawrence, Goodman Michael, Mittal Kriti, Morris David, Sieber Paul, Tutrone Ronald, Ryan Michael, Zhong Yi, Ufer Mike, Shore Neal
Urology San Antonio, 3327 Research Plaza Suite 403, San Antonio, TX, 78235, USA.
MidLantic Urology/Solaris Health, Bala Cynwyd, PA, USA.
Target Oncol. 2025 May;20(3):503-517. doi: 10.1007/s11523-025-01139-3. Epub 2025 Apr 4.
The gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix is the only oral androgen deprivation therapy (ADT) indicated for advanced prostate cancer (aPC). Combining ADT with androgen receptor signaling inhibitors (ARSIs) has shown improved clinical outcomes.
To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of relugolix in combination with ARSIs in patients with aPC.
In this 52-week, open-label study, patients received relugolix (120 mg once daily) with abiraterone (1,000 mg once daily) and corticosteroid (Part 1) or relugolix (240 mg once daily) with apalutamide (240 mg once daily) (Part 2). Metastatic castration-sensitive patients were eligible for both parts, whereas castration-resistant patients were eligible for Part 1 if metastatic and Part 2 if non-metastatic. Adverse events and other safety data were evaluated over 52 weeks, while pharmacodynamic and pharmacokinetic (Part 2 only) data were assessed over 12 weeks. Medication adherence to relugolix was measured by pill count.
Of 48 patients, 21 completed Part 1 and 20 completed Part 2. Most adverse events were grade 1 or 2, with hypertension (Part 1) and rash (Part 2) being most common. Mean testosterone concentrations remained below castrate level. Median prostate-specific antigen concentration was 0.04 ng/mL at week 12 in both parts. Concentrations of relugolix, apalutamide, and N-desmethyl-apalutamide were stable over 12 weeks similar to previous data. Relugolix adherence rates were > 97% in both parts.
The safety/tolerability profile of both combination therapies was consistent with those of the individual drugs. These findings support using relugolix in combination with abiraterone or apalutamide as treatment of aPC.
ClinicalTrials.gov identifier NCT04666129.
促性腺激素释放激素（GnRH）受体拮抗剂瑞卢戈利是唯一被批准用于晚期前列腺癌（aPC）的口服雄激素剥夺疗法（ADT）。将ADT与雄激素受体信号抑制剂（ARSIs）联合使用已显示出更好的临床疗效。
评估瑞卢戈利与ARSIs联合应用于aPC患者的安全性、耐受性、药代动力学和药效学。
在这项为期52周的开放标签研究中，患者接受瑞卢戈利（每日一次，120mg）联合阿比特龙（每日一次，1000mg）和皮质类固醇（第1部分），或瑞卢戈利（每日一次，240mg）联合阿帕他胺（每日一次，240mg）（第2部分）。转移性去势敏感患者两部分均符合条件，而去势抵抗患者如果是转移性的则符合第1部分条件，如果是非转移性的则符合第2部分条件。在52周内评估不良事件和其他安全性数据，而药效学和药代动力学（仅第2部分）数据在12周内进行评估。通过计数药丸来测量对瑞卢戈利的药物依从性。
48例患者中，21例完成第1部分，20例完成第2部分。大多数不良事件为1级或2级，最常见的是高血压（第1部分）和皮疹（第2部分）。平均睾酮浓度保持在去势水平以下。两部分在第12周时前列腺特异性抗原浓度中位数均为0.04ng/mL。瑞卢戈利、阿帕他胺和N-去甲基-阿帕他胺的浓度在12周内保持稳定，与先前数据相似。两部分中瑞卢戈利的依从率均>97%。
两种联合疗法的安全性/耐受性与各单药一致。这些发现支持将瑞卢戈利与阿比特龙或阿帕他胺联合用于治疗aPC。
ClinicalTrials.gov标识符NCT04666129。
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