Department of Nuclear Medicine, University Hospital Essen, Essen, Germany.
German Cancer Consortium, University Hospital Essen, Essen, Germany.
J Nucl Med. 2024 Jun 3;65(6):909-916. doi: 10.2967/jnumed.123.267321.
Prospective results have demonstrated favorable safety and efficacy of [Lu]Lu-PSMA radiopharmaceutical therapy for up to 6 cycles in men with metastatic castration-resistant prostate cancer. However, no systematic data are available outlining the feasibility of extended therapy beyond 6 cycles. We aim to evaluate the safety and efficacy of extended [Lu]Lu-PSMA radiopharmaceutical therapy in patients who have received more than 6 cycles. In total, 111 patients were included in this multicenter retrospective analysis. Based on individual decisions, patients underwent uninterrupted continuation of therapy (continuous treatment) or reexposure after a therapy break (rechallenge treatment) between 2014 and 2023. Overall survival, 50% prostate-specific antigen (PSA) decline (measured 8-12 wk after treatment initiation or rechallenge), PSMA PET response, and grades per Common Terminology Criteria for Adverse Events were assessed. χ tests, multivariable Cox regression analysis, and log-rank tests were applied for statistical analyses. Patients received extended treatment with [Lu]Lu-PSMA, either as a continuous treatment (43/111, 38.7%) or as a rechallenge (68/111, 61.3%) treatment, with median cumulative doses of 57.4 or 60.8 GBq, respectively. Overall survival from the initiation of [Lu]Lu-PSMA was 31.3, 23.2, and 40.2 mo for the entire cohort, the continuous treatment group, and the rechallenge treatment group, respectively. The initial 50% PSA decline was significantly higher in the retreated group than in the continuous group (57/63 [90.4%] vs. 26/42 [61.9%]; = 0.006). A 50% PSA decline was observed in 23 of 62 patients (37.1%) after the first rechallenge. The rate of grades 3-4 toxicity was comparable between continuous and rechallenge treatments (anemia, 7/43 [16.3%] vs. 13/68 [19.1%)], = 0.6; leukocytopenia, 1/43 [2.3%] vs. 2/67 [3.0%], = 0.3; thrombocytopenia, 3/43 [7.0%] vs. 3/68 [4.4%], = 0.3; renal, 2/43 [4.7%] vs. 5/68 [7.4%], = 0.2). Extended therapy with [Lu]Lu-PSMA is safe and has not been associated with increased grades 3-4 toxicity. Patient candidates for extended treatment experienced a favorable median survival of 31.3 mo from the first administration. Response under [Lu]Lu-PSMA rechallenge demonstrated preserved efficacy of [Lu]Lu-PSMA after a treatment break.
前瞻性结果表明，在转移性去势抵抗性前列腺癌男性中，[Lu]Lu-PSMA 放射性药物治疗进行 6 个周期以上具有良好的安全性和疗效。然而，尚无系统数据表明超过 6 个周期的延长治疗的可行性。我们旨在评估在接受超过 6 个周期治疗的患者中延长[Lu]Lu-PSMA 放射性药物治疗的安全性和疗效。
这项多中心回顾性分析共纳入 111 例患者。根据个体决策，患者在 2014 年至 2023 年间进行不间断的连续治疗（连续治疗）或治疗中断后重新暴露治疗（再挑战治疗）。评估总生存期、50%前列腺特异性抗原（PSA）下降（在治疗开始或再挑战后 8-12 周测量）、PSMA PET 反应和按常见不良事件术语标准分级。应用 χ 检验、多变量 Cox 回归分析和对数秩检验进行统计学分析。
患者接受了[Lu]Lu-PSMA 的延长治疗，无论是连续治疗（43/111，38.7%）还是再挑战治疗（68/111，61.3%），累积剂量中位数分别为 57.4 或 60.8GBq。从[Lu]Lu-PSMA 开始，整个队列、连续治疗组和再挑战治疗组的总生存期分别为 31.3、23.2 和 40.2 个月。初始 50% PSA 下降在再治疗组显著高于连续治疗组（57/63 [90.4%] vs. 26/42 [61.9%]； = 0.006）。在首次再挑战后，62 例患者中有 23 例（37.1%）观察到 50% PSA 下降。连续治疗和再挑战治疗的 3-4 级毒性发生率相当（贫血，7/43 [16.3%] vs. 13/68 [19.1%]）， = 0.6；白细胞减少症，1/43 [2.3%] vs. 2/67 [3.0%]， = 0.3；血小板减少症，3/43 [7.0%] vs. 3/68 [4.4%]， = 0.3；肾，2/43 [4.7%] vs. 5/68 [7.4%]， = 0.2）。
[Lu]Lu-PSMA 的延长治疗是安全的，并且与增加的 3-4 级毒性无关。接受延长治疗的患者候选者的中位总生存期为首次给药后的 31.3 个月。在[Lu]Lu-PSMA 再挑战下的反应表明，在治疗中断后，[Lu]Lu-PSMA 的疗效仍然保留。
