Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, 525 East 68th Street, Box 403, New York, NY, 10065, USA.
Department of Urology, Weill Cornell Medicine, New York, NY, USA.
Curr Oncol Rep. 2021 Mar 29;23(5):59. doi: 10.1007/s11912-021-01042-w.
Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) is a promising investigational treatment for metastatic castration-resistant prostate cancer (mCRPC). This review describes the available data with PSMA TRT.
Conjugates used for PSMA TRT include antibodies or small molecules PSMA-radiolabeled with beta (most commonly 177Lu) or alpha emitters (commonly 225Ac). 177Lu-J591 demonstrated accurate targeting of known metastatic sites, based on post-treatment scintigraphy, in study populations that were not selected for PSMA expression, with evidence of dose-response and dose-limiting myelosuppression. Early phase studies of 177Lu-PSMA-617 have demonstrated favorable adverse event profiles and signs of clinical activity as evidenced by PSA responses and other short-term outcomes. A phase II randomized study of 177Lu-PSMA-617 showed a superior PSA50 response rate (66 vs 37%) over cabazitaxel in patients with docetaxel-pretreated, progressive mCRPC selected by PSMA and FDG PET/CT scans. PSMA TRT is emerging as a promising investigational therapy for mCRPC. The first randomized data with 177Lu-PSMA-617 (phase 2) have been presented, and the first phase 3 trial has completed accrual with radiographic progression-free and overall survival as dual primary endpoints. Multiple additional phase 3 trials of PSMA-TRT are starting and studies investigating optimal patient selection and combination therapy continue.
前列腺特异性膜抗原（PSMA）靶向放射性核素治疗（TRT）是一种有前途的转移性去势抵抗性前列腺癌（mCRPC）的治疗方法。本文描述了 PSMA TRT 的现有数据。
用于 PSMA TRT 的结合物包括 PSMA 抗体或小分子，与β（最常见的是 177Lu）或α发射器（通常是 225Ac）放射性标记。177Lu-J591 根据治疗后闪烁扫描，在未选择 PSMA 表达的研究人群中准确靶向已知的转移部位，有剂量反应和剂量限制骨髓抑制的证据。177Lu-PSMA-617 的早期研究表明，在 PSA 反应和其他短期结果证实的临床活性方面，具有良好的不良事件概况。177Lu-PSMA-617 的 II 期随机研究表明，在 PSMA 和 FDG PET/CT 扫描选择的多西紫杉醇预处理、进展性 mCRPC 患者中，与 cabazitaxel 相比，PSA50 反应率（66%对 37%）更高。PSMA TRT 作为 mCRPC 的一种有前途的研究性治疗方法正在出现。第一个 177Lu-PSMA-617（二期）的随机数据已经公布，第一个三期试验已经完成入组，以无进展生存期和总生存期为双重主要终点。正在启动多项 PSMA-TRT 的 III 期临床试验，继续研究最佳患者选择和联合治疗。
