Purpose: The addition of androgen receptor pathway inhibitors (ARPIs) to androgen deprivation therapy (ADT), with or without docetaxel (Doc), is currently recommended for metastatic, hormone-sensitive prostate cancer (mHSPC). Recently, the ARANOTE trial evaluated the efficacy and safety of Darolutamide + ADT in this setting. We aimed to update a network meta-analysis (NMA) of these combination therapies.Methods: We conducted a systematic search for RCTs on systemic therapies for mHSPC using MEDLINE, Embase, and the Web of Science Core Collection in September 2024. An NMA utilizing random-effects models was performed to compare progression-free survival (PFS), overall survival (OS), and adverse event (AE) incidence (PROSPERO: CRD42024591458).Results: A total of 12 RCTs (n = 11,954) were included in our NMAs. Triplet therapies were associated with significant improvements in PFS compared to ARPI-based doublet therapies (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.59–0.93;p= 0.01), but the difference did not reach the conventional levels of statistical significance for OS (HR: 0.82; 95% CI: 0.67–1.01;p= 0.059). In a subset analysis, compared to ARPI-based doublet therapies, triplet therapies showed a significant improvement in PFS in patients with high-volume disease (HR: 0.64; 95% CI: 0.47–0.88;p< 0.01), whereas no significant improvement was observed in those with low-volume disease (HR: 0.86; 95% CI: 0.45–1.67;p= 0.7). No significant difference in grade ≥ 3 AEs was observed between triplet therapies and ARPI-based doublet therapies. The main limitations include patient heterogeneity and limited follow-up in some studies.Conclusions: Triplet therapies can improve the oncologic outcomes of patients with mHSPC compared to ARPI-based doublet therapies, without significantly increasing severe AEs. These findings warrant further confirmation in a head-to-head trial powered for overall survival.
目的：目前推荐在雄激素剥夺疗法（ADT）基础上联合雄激素受体通路抑制剂（ARPI），无论是否加用多西他赛（Doc），用于治疗转移性激素敏感性前列腺癌（mHSPC）。近期，ARANOTE试验评估了达罗他胺联合ADT在该背景下的疗效与安全性。本研究旨在更新关于这些联合疗法的网络荟萃分析（NMA）。 方法：我们于2024年9月系统检索了MEDLINE、Embase和Web of Science核心合集数据库中关于mHSPC全身治疗的随机对照试验。采用随机效应模型进行NMA，以比较无进展生存期（PFS）、总生存期（OS）和不良事件（AE）发生率（PROSPERO注册号：CRD42024591458）。 结果：我们的NMA共纳入12项随机对照试验（n = 11,954）。与基于ARPI的双联疗法相比，三联疗法与PFS的显著改善相关（风险比[HR]：0.74；95%置信区间[CI]：0.59–0.93；p = 0.01），但在OS方面的差异未达到传统统计学显著性水平（HR：0.82；95% CI：0.67–1.01；p = 0.059）。在亚组分析中，与基于ARPI的双联疗法相比，三联疗法在高瘤负荷患者中显示出PFS的显著改善（HR：0.64；95% CI：0.47–0.88；p < 0.01），而在低瘤负荷患者中未观察到显著改善（HR：0.86；95% CI：0.45–1.67；p = 0.7）。三联疗法与基于ARPI的双联疗法在≥3级AE发生率方面未观察到显著差异。主要局限性包括患者异质性以及部分研究的随访时间有限。 结论：与基于ARPI的双联疗法相比，三联疗法可改善mHSPC患者的肿瘤学结局，且未显著增加严重AE。这些发现有待在以后以总生存期为终点的头对头试验中进一步验证。
肿瘤(癌症)患者之家