Safety and Efficacy of Extended Therapy with 177LuLu-PSMA: A German Multicenter Study

Prospective results have demonstrated favorable safety and efficacy of 177LuLu-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 177LuLu-PSMA radiopharmaceutical therapy in patients who have received more than 6 cycles. Methods: 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. χ2 tests, multivariable Cox regression analysis, and log-rank tests were applied for statistical analyses. Results: Patients received extended treatment with 177LuLu-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 177LuLu-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%; P = 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%), P = 0.6; leukocytopenia, 1/43 2.3% vs. 2/67 3.0%, P = 0.3; thrombocytopenia, 3/43 7.0% vs. 3/68 4.4%, P = 0.3; renal, 2/43 4.7% vs. 5/68 7.4%, P = 0.2). Conclusion: Extended therapy with 177LuLu-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 177LuLu-PSMA rechallenge demonstrated preserved efficacy of 177LuLu-PSMA after a treatment break.