Urologic Oncology, Studienpraxis Urologie, Steinengrabenstr. 17, Nürtingen, 72622, Germany.
Urologic Oncology, Centre Hospitalier de L'Université de Montréal/CRCHUM, 900 Rue St-Denis, Porte R10-464, Montréal, Québec, H2X 0A9, Canada.
Eur J Cancer. 2018 Nov;103:78-87. doi: 10.1016/j.ejca.2018.08.010. Epub 2018 Sep 12.
Androgen deprivation therapy (ADT) has long been the gold standard for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Clinical trials have demonstrated significant survival benefits when docetaxel (DOC) or abiraterone acetate (AA) and prednisone (P) are added to ADT, necessitating comparison of these combination treatments.
A systematic review of randomised controlled trials (RCTs) of AA-/ADT-/DOC-containing treatment regimens in newly diagnosed patients with high-risk and/or high-volume mHSPC identified three RCTs (LATITUDE, CHAARTED and GETUG-AFU 15). Network meta-analyses (NMAs) using fixed effects Bayesian methods were performed to compare relative benefits of each treatment on overall survival (OS), radiographic progression-free survival (rPFS) and quality of life (QoL) measured by the Brief Pain Inventory, and the Functional Assessment of Cancer Therapy-Prostate questionnaire. One trial, STAMPEDE, was assessed in exploratory OS analyses.
The hazard ratio (HR) for OS ranged from 0.85 to 0.92, with the Bayesian probability of AA + P + ADT being better than DOC + ADT ranging between 72% and 87%. For rPFS, the HR ranged between 0.71 and 0.76 (Bayesian probability range: 93%-97%). Exploratory analyses including STAMPEDE found similar trends. AA + P + ADT also showed improved QoL compared with DOC + ADT for at least 1 year of therapy, with results being more pronounced at 3 months.
Our findings suggest that AA + P + ADT is at least as effective as DOC + ADT in reducing the risk of death in men with mHSPC and better at preventing disease progression and improving QoL. The NMA provides useful insights to clinicians and other decision-makers on the relative efficacy of treatment options for men with mHSPC.
雄激素剥夺疗法(ADT)一直是转移性激素敏感前列腺癌(mHSPC)患者的金标准。临床试验表明,当多西他赛(DOC)或阿比特龙醋酸酯(AA)和泼尼松(P)联合 ADT 时,显著提高了生存率,因此需要对这些联合治疗进行比较。
系统检索了新诊断的高危和/或大体积 mHSPC 患者接受 AA-/ADT-/DOC 联合治疗方案的随机对照试验(RCT),共确定了 3 项 RCT(LATITUDE、CHAARTED 和 GETUG-AFU 15)。采用固定效应贝叶斯方法进行网络荟萃分析(NMA),比较每种治疗方案在总生存(OS)、影像学无进展生存(rPFS)和生活质量(QoL)方面的相对获益,QoL 通过简短疼痛量表和癌症治疗功能评估-前列腺问卷进行评估。一项试验 STAMPEDE 用于探索性 OS 分析。
OS 的风险比(HR)范围为 0.85 至 0.92,AA+P+ADT 优于 DOC+ADT 的贝叶斯概率范围为 72%至 87%。rPFS 的 HR 范围为 0.71 至 0.76(贝叶斯概率范围:93%-97%)。包括 STAMPEDE 在内的探索性分析发现了相似的趋势。在至少 1 年的治疗期间,AA+P+ADT 与 DOC+ADT 相比也能改善 QoL,在 3 个月时更为明显。
我们的研究结果表明,AA+P+ADT 在降低 mHSPC 男性死亡风险方面至少与 DOC+ADT 一样有效,并且在预防疾病进展和改善 QoL 方面更有优势。NMA 为临床医生和其他决策者提供了有关 mHSPC 男性治疗选择相对疗效的有用见解。