Department of Urology, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China.
Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Br J Cancer. 2024 Nov;131(8):1363-1377. doi: 10.1038/s41416-024-02823-3. Epub 2024 Sep 2.
This systematic review and network meta-analysis aimed to assess the comparative effectiveness and safety profiles of current combination therapies based on androgen deprivation therapy (ADT) for the heterogeneous population of individuals with metastatic castration-sensitive prostate cancer (mCSPC).
We retrieved pertinent literature from PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov, and international conference databases. The study was registered in the Prospective Register of Systematic Reviews (CRD42023453853) for transparency.
Our analysis included 20 RCTs involving 14,995 patients, evaluating 15 ADT-based combinations, including systemic therapies, radiotherapy and surgery. In the overall population, the darolutamide triplet (DARO + docetaxel + ADT) demonstrated comparable overall survival (OS) benefits to prostatectomy/radical local therapy (RLT) plus ADT (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.43-1.57). Additionally, the enzalutamide (ENZ) triplet (ENZ + DOC + ADT) appeared to confer the best progression-free survival (HR, 0.34; 95% CI: 0.27-0.43). Subgroup analysis based on metastatic burden indicated that RLT plus ADT had the best OS performance in patients with low burden, while the DARO triplet was associated with the best OS in patients with high burden. Regarding adverse events (AEs), the addition of certain androgen receptor pathway inhibitor (ARPI) agents to ADT led to an increased incidence of severe AEs, while the addition of DOC to the ARPI doublet did not appear to elevate the exposure-adjusted incidence rates.
Our findings suggest that combined treatments result in better survival outcomes than does ADT alone. In the current landscape of systemic therapy, the significance of local therapy should not be underestimated, and therapeutic decisions should be tailored with meticulous consideration of clinical heterogeneity among patients.
本系统评价和网络荟萃分析旨在评估基于雄激素剥夺疗法 (ADT) 的当前联合治疗方案在转移性去势敏感前列腺癌 (mCSPC) 异质人群中的比较疗效和安全性。
我们从 PubMed、EMBASE、Cochrane 图书馆、ClinicalTrials.gov 和国际会议数据库中检索相关文献。该研究在系统评价前瞻性登记库 (CRD42023453853) 中进行了注册，以保证透明度。
我们的分析纳入了 20 项 RCT，涉及 14995 名患者，评估了 15 种基于 ADT 的联合治疗方法，包括系统治疗、放疗和手术。在总体人群中，达罗他胺三联疗法 (DARO + 多西他赛 + ADT) 在总生存期 (OS) 方面与前列腺切除术/根治性局部治疗 (RLT) + ADT 相当 (风险比 [HR]，0.82；95%置信区间 [CI]，0.43-1.57)。此外，恩扎卢胺 (ENZ) 三联疗法 (ENZ + DOC + ADT) 似乎能提供最佳的无进展生存期 (HR，0.34；95%CI：0.27-0.43)。基于转移负担的亚组分析表明，RLT + ADT 在低负担患者中具有最佳的 OS 表现，而 DARO 三联疗法与高负担患者的最佳 OS 相关。关于不良事件 (AE)，某些雄激素受体通路抑制剂 (ARPI) 药物联合 ADT 会导致严重 AE 的发生率增加，而将 DOC 加入 ARPI 双联疗法似乎不会增加调整后的暴露率。
我们的研究结果表明，联合治疗比单独 ADT 治疗能带来更好的生存结果。在当前的系统治疗领域，局部治疗的意义不应被低估，治疗决策应根据患者之间的临床异质性进行精心考虑。
