The phase 3 VISION trial demonstrated that [¹⁷⁷Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]–positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor–signaling inhibitors (ARSIs). The U.S. expanded-access program (EAP; NCT04825652) was opened to provide access to [¹⁷⁷Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. This study aimed to evaluate the efficacy and safety profile of [¹⁷⁷Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP at 4 institutions in the United States with available toxicity and outcome data were included. Outcome measures included OS, a prostate-specific antigen (PSA) response rate (RR) of at least 50%, and incidences of toxicity according to Common Terminology Criteria for Adverse Events version 5.0. Differences in baseline characteristics, outcome data, and toxicity between the EAP and VISION were evaluated using t testing of proportions and survival analyses. Results: In total, 117 patients with mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 within the EAP between May 2021 and March 2022 were eligible and included in this analysis. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; P < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; P < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; P = 0.15), thrombocytopenia (13% vs. 8%; P = 0.13), and neutropenia (3% vs. 3%; P = 0.85) and similar PSA RRs (42% vs. 46%; P = 0.50) and OS (median: 15.1 vs. 15.3 mo; P > 0.05). Conclusion: Patients with PSMA-positive mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 within the EAP were later in their disease trajectory than VISION patients. Patients enrolled in the EAP achieved similar PSA RRs and OS and had a safety profile similar to that of the VISION trial patients.

3 期 VISION 试验表明，[¹⁷⁷Lu]Lu-PSMA-617 延长了接受紫杉烷类化疗和雄激素受体信号抑制剂 （ARSI） 治疗后进展的前列腺特异性膜抗原 [PSMA] 阳性转移性去势抵抗性前列腺癌 （mCRPC） 患者的无进展生存期和总生存期 （OS）。美国扩大准入计划 （EAP;NCT04825652） 的开放旨在为符合条件的患者提供 [¹⁷⁷Lu]Lu-PSMA-617 的使用权，直到获得监管部门的批准。本研究旨在评估 [¹⁷⁷Lu]Lu-PSMA-617 在 EAP 中的疗效和安全性，并将结果与 VISION 试验的结果进行比较。方法：纳入在美国 4 个机构参加 EAP 且具有可用毒性和结局数据的患者。结局指标包括 OS、前列腺特异性抗原 （PSA） 反应率 （RR） 至少为 50%，以及根据不良事件通用术语标准 5.0 版的毒性发生率。使用比例 t 检验和生存分析评估 EAP 和 VISION 之间基线特征、结果数据和毒性的差异。结果：共有 117 例在 2021 年 5 月至 2022 年 3 月期间在 EAP 内接受 [¹⁷⁷Lu]Lu-PSMA-617 治疗的 mCRPC 患者符合条件并被纳入本分析。参加 EAP 的患者更频繁地接受 ARSI 预处理（≥2 种 ARSI 方案：70% 对 46%;P < 0.001） 和基线时体能状态较差 （Eastern Cooperative Oncology Group 评分 ≥ 2：19% vs. 7%;P < 0.001） 比 VISION 患者。EAP 和 VISION 患者的 3 级或更高级别贫血水平相似 （18% vs. 13%;P = 0。15），血小板减少症（13% vs. 8%;P = 0.13）和中性粒细胞减少症 （3% vs. 3%;P = 0.85）和类似的 PSA RR （42% vs. 46%;P = 0.50）和 OS （中位数：15.1 vs. 15.3 个月;P > 0.05）。结论：在 EAP 内接受 [¹⁷⁷Lu]Lu-PSMA-617 治疗的 PSMA 阳性 mCRPC 患者比 VISION 患者处于疾病轨迹中更晚。参加 EAP 的患者获得了相似的 PSA RR 和 OS，并且具有与 VISION 试验患者相似的安全性特征。