Radiation Oncology Section, Department of Surgical and Biomedical Science, University of Perugia, Italy.
Department of Radiation Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy.
Semin Oncol. 2022 Oct;49(5):409-418. doi: 10.1053/j.seminoncol.2022.09.005. Epub 2022 Sep 24.
Prostate cancer is the second most common cause of cancer-related mortality in men. In patients undergoing a failure after radical treatment, one of the therapeutic option is androgen deprivation: despite initial response rates, a progression to a state of castration resistance is observed in most of the patients. In the present article, we conducted a systematic review and meta-analysis of all clinical trials assessing treatment for nmCRPC with next-generation androgen receptor inhibitors. We performed a review and meta-analysis of phase III randomized controlled trials comparing new agents (apalutamide, enzalutamide, darolutamide) with placebo as control arm, in the setting of nmCRPC. Patients treated with next-generation ARIs had a 26% reduction in the risk of death compared with placebo; compared with other ARIs, darolutamide had the lowest rate of grade 3 and 4 AEs and the lowest therapy discontinuation rate due to any grade AEs. This meta-analysis shows that treatment with new ARIs is safe and significantly reduces the risk of death and of metastasis onset in nmCRPC patients. Under way studies on new biomarkers such as genomic classifiers will probably allow the stratification in more specific subsets of disease. New imaging modalities such as PSMA-PET have shown greater sensibility and specificity than conventional imaging in metastases detection. All patients were randomized in a 2:1 fashion, with a total of 2,694 who underwent next-generation ARIs (806 apalutamide, 955 darolutamide, 933 enzalutamide) and 1,423 in the placebo arm.
前列腺癌是男性癌症相关死亡的第二大常见原因。在接受根治性治疗后失败的患者中，一种治疗选择是去势治疗：尽管初始反应率高，但大多数患者都会出现去势抵抗进展。在本文中，我们对所有评估下一代雄激素受体抑制剂治疗 nmCRPC 的临床试验进行了系统评价和荟萃分析。我们对 III 期随机对照试验进行了综述和荟萃分析，比较了新药物（阿帕鲁胺、恩扎卢胺、达罗他胺）与安慰剂作为对照组在 nmCRPC 中的治疗效果。与安慰剂相比，接受下一代 ARI 治疗的患者死亡风险降低了 26%；与其他 ARIs 相比，达罗他胺的 3/4 级不良事件发生率最低，因任何级别不良事件导致的治疗停药率最低。这项荟萃分析表明，新一代 ARI 治疗是安全的，可显著降低 nmCRPC 患者的死亡风险和转移发生风险。正在进行的新生物标志物研究（如基因组分类器）可能会使疾病的亚组分层更加具体。新的成像方式（如 PSMA-PET）在转移检测中的敏感性和特异性均优于传统成像。所有患者均以 2:1 的比例随机分组，共有 2694 例患者接受了下一代 ARI（806 例阿帕鲁胺、955 例达罗他胺、933 例恩扎卢胺），1423 例患者接受了安慰剂治疗。
