Hoeh Benedikt, Wenzel Mike, Tian Zhe, Karakiewicz Pierre I, Saad Fred, Steuber Thomas, Graefen Markus, Tilki Derya, Herout Roman, Thomas Christian, Chun Felix K-H, Mandel Philipp
Department of Urology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.
Eur Urol Focus. 2024 Dec 5. doi: 10.1016/j.euf.2024.11.004.
The treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has been extended by another phase 3 randomized control trial (ARANOTE) demonstrating favorable outcomes of a doublet therapy combining the androgen receptor pathway inhibitor (ARPI) darolutamide with androgen deprivation therapy (ADT) over ADT monotherapy. Owing to differences in trial designs, patient enrollment, and most notably different control treatment regimens, we hereby present an updated network meta-analysis (NMA) embedding the doublet therapy with darolutamide within the current treatment regimens. In NMA-derived ranking, darolutamide and ADT showed similar oncological efficacy to the already known doublet therapies for progression-free survival (p = 0.49). These findings were consistent when solely doublet treatments, including apalutamide, enzalutamide, or darolutamide, were stratified according to disease volume. Overall survival (OS) data in ARANOTE are very immature, with up to date no significant differences in OS between the doublet regimen and the control group (hazard ratio: 0.81; 95% confidence interval: 0.59-1.12). The combination of darolutamide and ADT is likely-with the requirement of additional follow-up-to become another standard of care regimen for mHSPC following approval in the future. PATIENT SUMMARY: The phase 3 ARANOTE trial has shown the combination of darolutamide and androgen deprivation therapy (ADT) to have favorable outcomes for metastatic hormone-sensitive prostate cancer (mHSPC) over ADT monotherapy. This combination therapy was as effective as the already known doublet therapies for progression free-survival, and had a very favorable safety and toxicity profile. Following approval, the combination of darolutamide and ADT may become another standard of care regimen for mHSPC.
另一项3期随机对照试验（ARANOTE）扩展了转移性激素敏感性前列腺癌（mHSPC）的治疗前景，该试验表明，雄激素受体途径抑制剂（ARPI）达罗他胺与雄激素剥夺疗法（ADT）联合的双联疗法比ADT单药疗法具有更好的疗效。由于试验设计、患者入组情况不同，最显著的是对照治疗方案不同，我们在此呈现一项更新的网络荟萃分析（NMA），将达罗他胺双联疗法纳入当前治疗方案中。在NMA得出的排名中，达罗他胺和ADT在无进展生存期方面显示出与已知双联疗法相似的肿瘤学疗效（p = 0.49）。当仅根据疾病体积对包括阿帕他胺、恩杂鲁胺或达罗他胺在内的双联治疗进行分层时，这些结果是一致的。ARANOTE试验中的总生存期（OS）数据非常不成熟，截至目前，双联治疗方案与对照组之间的OS无显著差异（风险比：0.81；95%置信区间：0.59 - 1.12）。达罗他胺与ADT联合使用可能（需要进一步随访）在未来获批后成为mHSPC的另一种标准治疗方案。患者总结：3期ARANOTE试验表明，与ADT单药疗法相比，达罗他胺与雄激素剥夺疗法（ADT）联合使用对转移性激素敏感性前列腺癌（mHSPC）具有更好的疗效。这种联合疗法在无进展生存期方面与已知双联疗法一样有效，并且具有非常良好的安全性和毒性特征。获批后，达罗他胺与ADT联合使用可能成为mHSPC另一种标准治疗方案。
