Department of Nuclear Medicine, Saarland University - Medical Center, Kirrberger Str. 100, Geb. 50, D-66421, Homburg, Germany.
Department of Nuclear Medicine, Campus-Fulda, University of Marburg, Fulda, Germany.
Eur J Nucl Med Mol Imaging. 2024 Nov;51(13):4151-4162. doi: 10.1007/s00259-024-06825-4. Epub 2024 Jul 15.
Rechallenge of [Lu]Lu-PSMA-617 radioligand therapy (RLT) was proposed for patients who initially responded to PSMA-RLT experiencing partial remission, but relapsed into progression after a certain period of remission. However, only limited data is available regarding this approach. In this study, we analyzed the efficacy and safety profile of one or more series of [Lu]Lu-PSMA-617 RLT rechallenge in patients from a prospective registry (REALITY Study, NCT04833517) after they initially benefited from PSMA-RLT.
Forty-seven patients with metastatic castration-resistant prostate cancer (mCRPC) who had biochemical response to initial [Lu]Lu-PSMA-617 RLT followed by disease progression received at least one (up to three) series of [Lu]Lu-PSMA-617 RLT rechallenge. Biochemical response rates based on prostate-specific antigen (PSA) serum value, PSA-based progression-free survival (PFS) and overall survival (OS) were calculated. Adverse events of the treatment were assessed according to 'common terminology criteria for adverse events' (CTCAE).
After one series of RLT rechallenge, a PSA decline of at least 50% was achieved in 27/47 patients (57.4%). The median PFS of all patients was 8.7 mo and the median OS was 22.7 mo, each calculated from the administration of the first rechallenge series. Patients who responded (PSA decline > 50%) to the rechallenge showed a median OS of 27.3 mo. Regarding PFS, a significant correlation (r = 0.4128, p = 0.0323) was found for these patients comparing initial and rechallenge RLT. Ten patients received a second and 3 patients received a third rechallenge series with 8/10 and 3/3 patients responding to repeated RLT rechallenge. No severe deterioration of adverse events rated by CTCAE criteria was observed.
[Lu]Lu-PSMA-617 RLT rechallenge is associated with significant PSA response and encouraging survival outcome as well as a very favourable safety profile and should therefore be considered as a straight-forward treatment option in mCRPC patients, who previously benefited from PSMA-RLT.
对于最初对 PSMA-RLT 有反应但在缓解一定时间后复发的部分缓解的患者，提议重新使用 [Lu]Lu-PSMA-617 放射性配体治疗（RLT）。然而，关于这种方法，只有有限的数据。在这项研究中，我们分析了前瞻性登记研究（REALITY 研究，NCT04833517）中最初从 PSMA-RLT 中受益的患者接受一次或多次 [Lu]Lu-PSMA-617 RLT 重新挑战后的疗效和安全性。
47 例转移性去势抵抗性前列腺癌（mCRPC）患者在接受初始 [Lu]Lu-PSMA-617 RLT 后出现生化反应，随后出现疾病进展，他们至少接受了一次（最多三次）[Lu]Lu-PSMA-617 RLT 重新挑战。根据前列腺特异性抗原（PSA）血清值计算生化反应率，根据 PSA 计算无进展生存（PFS）和总生存（OS）。根据“不良事件通用术语标准”（CTCAE）评估治疗的不良反应。
在一次 RLT 重新挑战后，47 例患者中有 27/47 例（57.4%）PSA 下降至少 50%。所有患者的中位 PFS 为 8.7 个月，中位 OS 为 22.7 个月，分别从第一次重新挑战系列开始计算。对重新挑战有反应（PSA 下降>50%）的患者的中位 OS 为 27.3 个月。关于 PFS，对这些患者进行比较，发现初始 RLT 和重新挑战 RLT 之间存在显著相关性（r=0.4128，p=0.0323）。10 例患者接受了第二次和 3 例患者接受了第三次重新挑战系列，8/10 例和 3/3 例患者对重复 RLT 重新挑战有反应。未观察到 CTCAE 标准评定的严重不良反应恶化。
[Lu]Lu-PSMA-617 RLT 重新挑战与显著的 PSA 反应和令人鼓舞的生存结果相关，且具有良好的安全性，因此应考虑作为先前从 PSMA-RLT 中获益的 mCRPC 患者的直接治疗选择。
