CONTEXT There have been substantial changes in the management of men with metastatic hormone-sensitive prostate cancer (mHSPC) over the past 5 yr, with upfront combination therapies replacing androgen-deprivation therapy (ADT) alone. A range of therapies have entered the space with no clear answer regarding their comparative efficacy. OBJECTIVE To perform a systematic review and network meta-analysis to characterise the comparative efficacy of combination approaches in men with mHSPC. EVIDENCE ACQUISITION We searched multiple databases and abstracts of major meetings up to June 2019 for randomised trials of patients receiving first-line therapy for metastatic disease, a combination of ADT and one (or more) of taxane-based chemotherapy, and androgen receptor-targeted therapies. The primary endpoint was overall survival (OS) and we evaluated progression-free survival as a secondary outcome. We performed subgroup analysis based on the volume of disease. EVIDENCE SYNTHESIS We found seven trials that met our eligibility criteria using either docetaxel, abiraterone acetate, enzalutamide, or apalutamide in combination with ADT. All agents in combination with ADT were shown to be superior to ADT alone; enzalutamide + ADT had the lowest absolute hazard ratio compared with ADT only (hazards ratio 0.53, 95% confidence interval 0.37-0.75), and an estimated 76.9% probability that it is the preferred treatment to prolong OS compared with other combination treatments, or with ADT alone. Enzalutamide appeared to have better OS compared with docetaxel in men with low-volume disease, but there was no difference in other comparisons. CONCLUSIONS Combination therapy with any of docetaxel, abiraterone acetate, enzalutamide, or apalutamide provides a significant OS benefit when compared with ADT alone. We did not identify significant differences in OS between different combination therapies. Subtle differences between these options provide clinicians considerable flexibility when selecting options for individual patients. PATIENT SUMMARY Many men with metastatic, hormone-sensitive prostate cancer should be managed with upfront combination therapy instead of androgen-deprivation therapy alone. Clinicians may consider many factors during the decision-making process, and thus management should be tailored for patients individually.

中文翻译：

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转移性激素敏感性前列腺癌联合治疗方法之间疗效的间接比较：系统评价和网络荟萃分析。

上下文在过去的5年中，转移性激素敏感性前列腺癌（mHSPC）的男性管理发生了巨大变化，前瞻性联合疗法替代了单独的雄激素剥夺疗法（ADT）。一系列疗法已进入该领域，但它们的相对疗效尚无明确答案。目的进行系统的回顾和网络荟萃分析，以表征联合治疗方法在mHSPC男性中的比较疗效。证据采集我们搜索了截至2019年6月的多个数据库和主要会议摘要，以研究接受转移性疾病一线治疗，ADT和一种或多种紫杉烷类化学疗法以及雄激素受体靶向治疗的患者的随机试验疗法。主要终点是总体生存期（OS），我们将无进展生存期评估为次要结果。我们根据疾病量进行了亚组分析。证据综合我们发现使用多西他赛，乙酸阿比特龙酯，恩杂鲁胺或阿帕鲁胺与ADT联合使用的七项试验均符合我们的入选标准。已证明所有与ADT联合使用的药物均优于单独使用ADT的药物。与仅使用ADT相比，enzalutamide + ADT的绝对危险比最低（危险比0.53，95％置信区间0.37-0.75），与其他联合治疗或与其他联合治疗相比，它是延长OS的首选治疗方法估计为76.9％的可能性仅ADT。与多西他赛相比，恩扎鲁胺在低容量疾病男性中的OS更好，但在其他比较中没有差异。结论与单独的ADT相比，多西他赛，醋酸阿比特龙，恩杂鲁胺或阿帕鲁胺中的任何一种联合治疗均可显着改善OS。我们没有发现不同组合疗法之间的OS有显着差异。这些选择之间的细微差别为临床医生为个别患者选择选择时提供了相当大的灵活性。患者总结许多患有转移性，激素敏感型前列腺癌的男性应接受前期联合治疗，而不是单独进行雄激素剥夺治疗。临床医生可能会在决策过程中考虑许多因素，因此应针对患者量身定制管理方案。与单独使用ADT相比，Apalutamide或apalutamide具有明显的OS益处。我们没有发现不同组合疗法之间的OS有显着差异。这些选择之间的细微差异为临床医生在为个别患者选择选择时提供了相当大的灵活性。患者总结许多患有转移性，激素敏感型前列腺癌的男性应接受预先联合治疗，而不是单独进行雄激素剥夺治疗。临床医生可能会在决策过程中考虑许多因素，因此应针对患者量身定制管理方案。与单独使用ADT相比，Apalutamide或apalutamide具有明显的OS益处。我们没有发现不同组合疗法之间的OS有显着差异。这些选择之间的细微差异为临床医生在为个别患者选择选择时提供了相当大的灵活性。患者总结许多患有转移性，激素敏感型前列腺癌的男性应接受前期联合治疗，而不是单独进行雄激素剥夺治疗。临床医生可能会在决策过程中考虑许多因素，因此应针对患者量身定制管理方案。患者总结许多患有转移性，激素敏感型前列腺癌的男性应接受前期联合治疗，而不是单独进行雄激素剥夺治疗。临床医生可能会在决策过程中考虑许多因素，因此应针对患者量身定制管理方案。患者总结许多患有转移性，激素敏感型前列腺癌的男性应接受前期联合治疗，而不是单独进行雄激素剥夺治疗。临床医生可能会在决策过程中考虑许多因素，因此应针对患者量身定制管理方案。