A Single-Arm, Low-Dose, Prospective Study of 177Lu-EB-PSMA Radioligand Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer
A Single-Arm, Low-Dose, Prospective Study of 177Lu-EB-PSMA Radioligand Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer
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DOI：
10.2967/jnumed.122.264857
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发表时间：
2022-11
期刊：
影响因子：
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通讯作者：
Guochang Wang;J. Zang;Yuanyuan Jiang;Qingxing Liu;Huimin Sui;Rongxi Wang;Xinrong Fan;Jingjing Zhang;Zhaohui Zhu;Xiaoyuan Shawn Chen-
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文献类型：
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作者：
Guochang Wang;J. Zang;Yuanyuan Jiang;Qingxing Liu;Huimin Sui;Rongxi Wang;Xinrong Fan;Jingjing Zhang;Zhaohui Zhu;Xiaoyuan Shawn Chen-
视觉摘要我们的目的是研究放射性配体治疗（RLT）的177 Lu-EB-前列腺特异性膜抗原（PSMA）的转移性去势抵抗性前列腺癌患者的安全性和疗效。研究方法：30例既往接受过紫杉烷类化疗和第二代雄激素剥夺治疗的进展性转移性去势抵抗性前列腺癌男性患者入组。所有患者以8周间隔接受多达3个周期的约2.0 GBq（55 mCi）177 Lu-EB-PSMA/周期。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疗效，包括前列腺特异性抗原（PSA）反应和分子成像反应。次要终点为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。结果：从2019年1月至2021年12月，分别有30、22和11例患者接受了1、2或3个周期的177 Lu-EB-PSMA RLT。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例（56.7%）患者的PSA降低至少50%。中位PSA PFS为4.6个月（95% CI，2.7-6.5个月），中位OS为12.6个月（95% CI，8.1-17.1个月）。较高的全身PSMA SUV平均值与较好的PSA缓解相关，较高的基线碱性磷酸酶和较大的PSMA阳性肿瘤总体积与较差的PSA PFS相关，存在内脏转移和基线时较高的PSA值是OS较差的显著因素。177 Lu-EB-PSMA RLT后，健康相关的生活质量结局显著改善。结论：基于约2.0 GBq的177 Lu-EB-PSMA长达3个周期的RLT可实现与7.4-GBq剂量的177 Lu-PSMA-617长达4-6个周期的PSA应答和血液学毒性相当的PSA应答和血液学毒性。需要更多177 Lu-EB-PSMA RLT周期的进一步研究，以评估PFS和OS方面的潜在获益。
Visual Abstract We aimed to investigate the safety and therapeutic efficacy of radioligand therapy (RLT) of 177Lu-EB-prostate-specific membrane antigen (PSMA) in patients with metastatic castration-resistant prostate cancer. Methods: 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 177Lu-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. Results: From January 2019 to December 2021, 30, 22, and 11 patients received 1, 2, or 3 cycles of 177Lu-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 SUVmean 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 177Lu-EB-PSMA RLT. Conclusion: RLT based on approximately 2.0 GBq of 177Lu-EB-PSMA for up to 3 cycles may achieve a PSA response and hematologic toxicity comparable to those from 7.4-GBq doses of 177Lu-PSMA-617 for up to 4–6 cycles. Further studies with more cycles of 177Lu-EB-PSMA RLT are needed to evaluate the potential benefits in terms of PFS and OS.