Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
Department of Medical Oncology, B.R. Ambedkar Institute Rotary Cancer Hospital (B.R.A.I.R.C.H.), All India Institute of Medical Sciences, New Delhi, 110029, India.
Eur J Nucl Med Mol Imaging. 2024 Jul;51(8):2495-2503. doi: 10.1007/s00259-024-06677-y. Epub 2024 Mar 12.
The use of [Lu]Lu-PSMA-617 radioligand therapy has become increasingly recognized as a viable therapeutic approach for patients in the advanced stages of metastatic castration-resistant prostate cancer (mCRPC). However, there is limited data regarding its effectiveness and safety in earlier lines. This study aims to present our institution's experience with [Lu]Lu-PSMA-617 as a first-line systemic therapy for mCRPC.
We collected and analyzed data from consecutive mCRPC patients who underwent first-line treatment with [Lu]Lu-PSMA-617 at our center from 2015 to 2023. The various outcome measures included best prostate-specific antigen-response rate (PSA-RR) (proportion of patients achieving a ≥ 50% decline in PSA); objective radiographic response rate (ORR) (proportion of patients achieving complete or partial radiographic responses); radiographic progression-free survival (rPFS) (measured from treatment initiation until radiographic progression or death from any cause); overall survival (OS) (measured from treatment initiation until death from any cause); and adverse events.
Forty treatment-naïve mCRPC patients with PSMA-positive disease on [Ga]Ga-PSMA-11 PET/CT were included (median age: 68.5 years, range: 45-78; median PSA: 41 ng/mL, range: 1-3028). These patients received a median cumulative activity of 22.2 GBq (range: 5.55-44.4) [Lu]Lu-PSMA-617 over 1-6 cycles at 8-12 week intervals. A ≥ 50% decline in PSA was observed in 25/40 (62.5%) patients (best PSA-RR). Radiographic responses were evaluated for thirty-eight patients, with thirteen showing partial responses (ORR 34.2%). Over a median follow-up of 36 months, the median rPFS was 12 months (95% confidence interval, CI: 9-15), and the median OS was 17 months (95% CI: 12-22). Treatment-emergent grade ≥ 3 anemia, leucopenia, and thrombocytopenia were noted in 4/40 (10%), 1/40 (2.5%), and 3/40 (7.5%) patients, respectively.
The findings suggest that [Lu]Lu-PSMA-617 is a safe and effective option as a first-line treatment in mCRPC. Further trials are needed to definitively establish its role as an upfront treatment modality in this setting.
镥[^157^]Lu-PSMA-617 放射性配体疗法已被越来越多地认为是转移性去势抵抗性前列腺癌（mCRPC）晚期患者的可行治疗方法。然而，关于其在早期阶段的有效性和安全性的数据有限。本研究旨在介绍我们机构在 mCRPC 患者中应用镥[^157^]Lu-PSMA-617 作为一线系统治疗的经验。
我们收集并分析了 2015 年至 2023 年期间在我们中心接受一线镥[^157^]Lu-PSMA-617 治疗的连续 mCRPC 患者的数据。各种疗效指标包括最佳前列腺特异性抗原反应率（PSA-RR）（达到 PSA 下降≥50%的患者比例）；客观放射学反应率（ORR）（达到完全或部分放射学反应的患者比例）；放射学无进展生存期（rPFS）（从治疗开始到放射学进展或任何原因导致的死亡）；总生存期（OS）（从治疗开始到任何原因导致的死亡）；以及不良事件。
40 名治疗初治的 mCRPC 患者，在[Ga]Ga-PSMA-11 PET/CT 上有 PSMA 阳性疾病，（中位年龄：68.5 岁，范围：45-78；中位 PSA：41ng/mL，范围：1-3028）。这些患者接受了 22.2GBq（范围：5.55-44.4）的中位累积[Lu]Lu-PSMA-617 活性，在 8-12 周的间隔内进行 1-6 个周期。40 名患者中有 25 名（62.5%）PSA 下降≥50%（最佳 PSA-RR）。对 38 名患者进行了放射学反应评估，其中 13 名患者出现部分反应（ORR 34.2%）。在中位随访 36 个月期间，中位 rPFS 为 12 个月（95%置信区间，CI：9-15），中位 OS 为 17 个月（95%CI：12-22）。治疗后出现 40 名患者中≥3 级贫血（10%）、白细胞减少（2.5%）和血小板减少（7.5%）。
结果表明，[Lu]Lu-PSMA-617 作为 mCRPC 的一线治疗是一种安全有效的选择。需要进一步的试验来明确其作为该治疗方案的一线治疗方式的作用。
[^157^Lu]Lu-PSMA-617：镥[^157^]Lu-PSMA-617
