Wang Guochang, Zang Jie, Jiang Yuanyuan, Liu Qingxing, Sui Huimin, Wang Rongxi, Fan Xinrong, Zhang Jingjing, Zhu Zhaohui, Chen Xiaoyuan
Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Department of Nuclear Medicine, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
J Nucl Med. 2023 Apr;64(4):611-617. doi: 10.2967/jnumed.122.264857. Epub 2022 Nov 3.
We aimed to investigate the safety and therapeutic efficacy of radioligand therapy (RLT) of Lu-EB-prostate-specific membrane antigen (PSMA) in patients with metastatic castration-resistant prostate cancer. Thirty men with progressive metastatic castration-resistant prostate cancer previously treated with taxane-based chemotherapy and second-generation androgen deprivation therapy were enrolled. All patients received up to 3 cycles of approximately 2.0 GBq (55 mCi) of Lu-EB-PSMA per cycle at 8-wk intervals. The primary endpoint was therapeutic safety, including changes in hematologic status, liver function, and renal function. An additional primary endpoint was therapeutic efficacy, including prostate-specific antigen (PSA) response and molecular imaging response. The secondary endpoints were PSA progression-free survival (PFS) and overall survival (OS). Another endpoint was patient-reported health-related quality of life. From January 2019 to December 2021, 30, 22, and 11 patients received 1, 2, or 3 cycles of Lu-EB-PSMA RLT, respectively. During the entire follow-up period, 33.3% of patients experienced grade 3 hematologic adverse events. Seventeen (56.7%) patients achieved a PSA reduction of at least 50%. The median PSA PFS was 4.6 mo (95% CI, 2.7-6.5 mo), and the median OS was 12.6 mo (95% CI, 8.1-17.1 mo). A higher whole-body PSMA SUV correlated with a better PSA response, higher baseline alkaline phosphatase and larger total PSMA-positive tumor volume were associated with worse PSA PFS, and the existence of visceral metastases and higher PSA value at baseline were significant prognosticators of worse OS. Health-related quality-of-life outcomes improved significantly after Lu-EB-PSMA RLT. RLT based on approximately 2.0 GBq of Lu-EB-PSMA for up to 3 cycles may achieve a PSA response and hematologic toxicity comparable to those from 7.4-GBq doses of Lu-PSMA-617 for up to 4-6 cycles. Further studies with more cycles of Lu-EB-PSMA RLT are needed to evaluate the potential benefits in terms of PFS and OS.
我们旨在研究镥-依博素-前列腺特异性膜抗原（PSMA）放射性配体疗法（RLT）在转移性去势抵抗性前列腺癌患者中的安全性和治疗效果。招募了30名先前接受过紫杉烷类化疗和第二代雄激素剥夺疗法且病情进展的转移性去势抵抗性前列腺癌男性患者。所有患者每8周接受最多3个周期的治疗，每个周期给予约2.0 GBq（55 mCi）的镥-依博素-PSMA。主要终点是治疗安全性，包括血液学状态、肝功能和肾功能的变化。另一个主要终点是治疗效果，包括前列腺特异性抗原（PSA）反应和分子成像反应。次要终点是PSA无进展生存期（PFS）和总生存期（OS）。另一个终点是患者报告的健康相关生活质量。从2019年1月至2021年12月，分别有30、22和11名患者接受了1、2或3个周期的镥-依博素-PSMA RLT治疗。在整个随访期间，33.3%的患者发生了3级血液学不良事件。17名（56.7%）患者的PSA降低了至少50%。PSA PFS的中位数为4.6个月（95%CI，2.7 - 6.5个月），OS的中位数为12.6个月（95%CI，8.1 - 17.1个月）。全身PSMA标准化摄取值（SUV）越高，PSA反应越好；基线碱性磷酸酶越高和总PSMA阳性肿瘤体积越大，与PSA PFS越差相关；内脏转移灶的存在和基线时较高的PSA值是OS较差的显著预后因素。镥-依博素-PSMA RLT治疗后，健康相关生活质量结果有显著改善。基于约2.0 GBq的镥-依博素-PSMA进行最多3个周期的RLT，可能实现与7.4 GBq剂量的镥-PSMA-617进行最多4 - 6个周期治疗相当的PSA反应和血液学毒性。需要对更多周期的镥-依博素-PSMA RLT进行进一步研究，以评估其在PFS和OS方面的潜在益处。
