From the Departments of Nuclear Medicine.
Medical Oncology.
Clin Nucl Med. 2020 Jan;45(1):19-31. doi: 10.1097/RLU.0000000000002833.
The aim of this study was to evaluate the efficacy and safety of Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC).
In this prospective, single-arm, single-institutional study, 90 mCRPC patients with progressive disease (PD) on second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic Ga-PSMA-HBED-CC PET/CT, prior to inclusion for therapy. Included patients underwent Lu-PSMA-617 therapy at 8- to 12-weekly intervals. The primary end point was to assess the overall survival. The secondary and cosecondary end points included biochemical response assessment as per the Prostate Cancer Working Group 3 criteria, progression-free survival, radiological and molecular response criteria, clinical response, safety profile, and disease control rates. All the outcome parameters were evaluated in 90 patients except for the radiographic and molecular response, which was evaluated in 69 patients.
The median age of patients was 66.5 years (range, 30-88 years). The median activity administered per cycle was 3.7 to 8 GBq ranging from 1 to 7 cycles, and patients were followed up over a median duration of 28 months. At 2- to 3-month interval after the first therapy and the end of the assessment, greater than 50% decline in prostate-specific antigen was observed in 32.2% and 45.5%, respectively. Univariate analysis did not reveal any variables such as prior therapies, laboratory parameters, concomitant hormonal therapy, and SUV patient parameters associated with prostate-specific antigen decline. Radiographic response by diagnostic CT revealed partial remission in 23% (16/69), stable disease in 54% (37/69), and PD in 23% (16/69) of patients. Molecular tumor response by PET Response Criteria in Solid Tumor 1 criteria revealed 19 (27.5%) of 69 patients with partial remission, 30 (43.5%) of 69 with stable disease, and 20 (29%) of 69 with PD. The disease control rates according to the radiographic and molecular response were 77% and 71%, respectively. The median overall survival and median progression-free survivals were 14 and 11.8 months, respectively. Toxicities related to radioligand therapy were low and transient with no serious adverse effects.
Lu-PSMA-617 radionuclide therapy is a safe and effective approach to the treatment of mCRPC patients.
本研究旨在评估 Lu-PSMA-617 放射性配体疗法在转移性去势抵抗性前列腺癌（mCRPC）中的疗效和安全性。
在这项前瞻性、单臂、单中心研究中，招募了 90 名在二线激素治疗和/或多西他赛化疗中出现进展性疾病（PD）的 mCRPC 患者进行研究。所有患者在接受治疗前均进行了 Ga-PSMA-HBED-CC PET/CT 诊断。纳入的患者每 8-12 周接受 Lu-PSMA-617 治疗。主要终点是评估总生存期。次要终点和次要终点包括根据前列腺癌工作组 3 标准评估生化反应、无进展生存期、影像学和分子反应标准、临床反应、安全性概况和疾病控制率。除了在 69 名患者中评估的放射性和分子反应外，所有 90 名患者均评估了所有其他结果参数。
患者的中位年龄为 66.5 岁（范围，30-88 岁）。每个周期给予的中位活性为 3.7 至 8GBq，范围为 1 至 7 个周期，中位随访时间为 28 个月。在第一次治疗后 2-3 个月和评估结束时，分别有 32.2%和 45.5%的患者观察到前列腺特异性抗原下降超过 50%。单变量分析未发现任何与前列腺特异性抗原下降相关的变量，如既往治疗、实验室参数、同时进行的激素治疗和患者 SUV 参数。诊断 CT 的影像学反应显示，23%（16/69）的患者部分缓解，54%（37/69）的患者稳定疾病，23%（16/69）的患者进展。根据实体瘤 PET 反应标准 1 标准的分子肿瘤反应显示，69 名患者中有 19 名（27.5%）部分缓解，30 名（43.5%）稳定疾病，20 名（29%）进展。根据影像学和分子反应的疾病控制率分别为 77%和 71%。中位总生存期和中位无进展生存期分别为 14 个月和 11.8 个月。放射性配体治疗相关的毒性低且短暂，无严重不良事件。
Lu-PSMA-617 放射性核素疗法是治疗 mCRPC 患者的一种安全有效的方法。
