Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Center for Drug Safety and Effectiveness, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
JAMA Oncol. 2021 Mar 1;7(3):412-420. doi: 10.1001/jamaoncol.2020.6973.
Multiple systemic treatments are available for metastatic castration-sensitive prostate cancer (mCSPC), with unclear comparative effectiveness and safety and widely varied costs.
To compare the effectiveness and safety determined in randomized clinical trials of systemic treatments for mCSPC.
Bibliographic databases (MEDLINE, Embase, and Cochrane Central), regulatory documents (US Food and Drug Administration and European Medicines Agency), and trial registries (ClinicalTrials.gov and European Union clinical trials register) were searched from inception through November 5, 2019.
STUDY SELECTION, DATA EXTRACTION, AND SYNTHESIS: Eligible studies were randomized clinical trials evaluating the addition of docetaxel, abiraterone acetate, apalutamide, or enzalutamide to androgen-deprivation therapy (ADT) for treatment of mCSPC. Two investigators independently performed screening. Discrepancies were resolved through consensus. A Cochrane risk-of-bias tool was used to assess trial quality. Relative effects of competing treatments were assessed by bayesian network meta-analysis and survival models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used.
Overall survival, radiographic progression-free survival, and serious adverse events (SAEs).
Seven trials with 7287 patients comparing 6 treatments (abiraterone acetate, apalutamide, docetaxel, enzalutamide, standard nonsteroidal antiandrogen, and placebo/no treatment) were identified. Ordered from the most to the least effective determined by results of clinical trials, treatments associated with improved overall survival when added to ADT included abiraterone acetate (hazard ratio [HR], 0.61; 95% credible interval [CI], 0.54-0.70), apalutamide (HR, 0.67; 95% CI, 0.51-0.89), and docetaxel (HR, 0.79; 95% CI, 0.71-0.89); treatments associated with improved radiographic progression-free survival when added to ADT included enzalutamide (HR, 0.39; 95% CI, 0.30-0.50), apalutamide (HR, 0.48; 95% CI, 0.39-0.60), abiraterone acetate (HR, 0.51; 95% CI, 0.45-0.58), and docetaxel (HR, 0.67; 95% CI 0.60-0.74). Docetaxel was associated with substantially increased SAEs (odds ratio, 23.72; 95% CI, 13.37-45.15), abiraterone acetate with slightly increased SAEs (odds ratio, 1.42; 95% CI, 1.10-1.83), and other treatments with no significant increase in SAEs. Risk of bias was noted for 4 trials with open-label design, 3 trials with missing data, and 2 trials with potential unprespecified analyses.
In this network meta-analysis, as add-on treatments to ADT, abiraterone acetate and apalutamide may provide the largest overall survival benefits with relatively low SAE risks. Although enzalutamide may improve radiographic progression-free survival to the greatest extent, longer follow-up is needed to examine the overall survival benefits associated with enzalutamide.
对于转移性去势敏感型前列腺癌（mCSPC），有多种全身治疗方法，其疗效和安全性尚不明确，且费用差异很大。
比较 mCSPC 全身治疗的随机临床试验中确定的疗效和安全性。
从建库到 2019 年 11 月 5 日，检索了书目数据库（MEDLINE、Embase 和 Cochrane 中央）、监管文件（美国食品和药物管理局和欧洲药品管理局）和试验注册处（ClinicalTrials.gov 和欧盟临床试验注册处）。
研究选择、数据提取和综合：合格的研究是评估多西他赛、阿比特龙醋酸酯、阿帕鲁胺或恩扎卢胺联合去势治疗（ADT）治疗 mCSPC 的添加治疗的随机临床试验。两名调查员独立进行筛选。通过共识解决差异。使用 Cochrane 风险偏倚工具评估试验质量。通过贝叶斯网络荟萃分析和生存模型评估竞争治疗的相对效果。使用系统评价和荟萃分析的首选报告项目指南。
总生存、放射性无进展生存和严重不良事件（SAE）。
共纳入 7 项涉及 7287 例患者的试验，比较了 6 种治疗方法（阿比特龙醋酸酯、阿帕鲁胺、多西他赛、恩扎卢胺、标准非甾体抗雄激素和安慰剂/无治疗）。根据临床试验结果，从最有效到最无效的顺序排列，添加 ADT 后与改善总生存相关的治疗方法包括阿比特龙醋酸酯（风险比 [HR]，0.61；95%可信区间 [CI]，0.54-0.70）、阿帕鲁胺（HR，0.67；95%CI，0.51-0.89）和多西他赛（HR，0.79；95%CI，0.71-0.89）；添加 ADT 后与改善放射性无进展生存相关的治疗方法包括恩扎卢胺（HR，0.39；95%CI，0.30-0.50）、阿帕鲁胺（HR，0.48；95%CI，0.39-0.60）、阿比特龙醋酸酯（HR，0.51；95%CI，0.45-0.58）和多西他赛（HR，0.67；95%CI，0.60-0.74）。多西他赛与明显增加的 SAE（比值比，23.72；95%CI，13.37-45.15）相关，阿比特龙醋酸酯与稍高的 SAE（比值比，1.42；95%CI，1.10-1.83）相关，其他治疗方法则没有明显增加 SAE。4 项试验存在开放性标签设计、3 项试验存在数据缺失和 2 项试验存在潜在未指定分析的偏倚风险。
在这项网络荟萃分析中，作为 ADT 的附加治疗，阿比特龙醋酸酯和阿帕鲁胺可能具有最大的总生存获益，同时相对较低的 SAE 风险。虽然恩扎卢胺可能在最大程度上改善放射性无进展生存，但需要更长时间的随访来检查恩扎卢胺相关的总生存获益。
