MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK; University Hospitals Sussex NHS Foundation Trust, Royal Sussex County Hospital, Brighton, UK.
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK.
Clin Oncol (R Coll Radiol). 2024 Jan;36(1):e11-e19. doi: 10.1016/j.clon.2023.10.054. Epub 2023 Nov 8.
Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer.
The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately.
Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited.
Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.
雄激素剥夺疗法（ADT）通常通过黄体生成素释放激素类似物（LHRHa）实现，是前列腺癌管理的核心。LHRHa 降低了睾丸激素和雌激素水平，与显著的长期毒性有关。以前使用口服雌激素作为 ADT 因心血管毒性而被限制。经皮雌激素（tE2）贴片是一种潜在的替代 ADT，抑制睾丸激素而不引起相关的雌激素耗竭毒性（骨质疏松症、热潮红、代谢异常）和避免心血管毒性，我们在这里描述它们在前列腺癌男性中的评估。
PATCH（NCT00303784）适应性试验计划（通过 STAMPEDE [NCT00268476]平台纳入招募）正在评估 tE2 贴片作为前列腺癌男性 ADT 的安全性和有效性。一项最初的随机（LHRHa 与 tE2）二期研究（n=251）以心血管毒性为主要终点，现已扩展为三期评估。那些患有局部晚期（M0）或转移性（M1）前列腺癌的人有资格参加。为了反映管理和预后的变化，PATCH 计划现在分别评估这些队列。
招募工作已经完成，M0 队列和 M1 队列分别有 1362 名和 1128 名患者。tE2 的雄激素抑制率与 LHRHa 相当，代谢参数、生活质量和骨健康指标得到改善（腰椎骨密度的平均绝对变化为 LHRHa 为-3.0%，tE2 为+7.9%，估计臂间差异为 9.3%（95%置信区间 5.3-13.4）。重要的是，两种药物的心血管事件发生率没有显著差异，两组之间首次心血管事件的时间也没有差异（风险比 1.11，95%置信区间 0.80-1.53；P=0.54）。正在等待肿瘤学结果。
预计 2023 年最后一个季度将获得 M0 队列（无转移生存的主要终点）的疗效结果。对于 M1 患者（总生存的主要终点），正在探索使用限制性平均生存时间的分析。正在进行纵向样本的联合转化工作。
