A single-arm, low-dose, prospective study of 177 Lu-EB-PSMA radioligand therapy in patients with metastatic castration-resistant prostate cancer.

We aimed to investigate the safety and therapeutic efficacy of radioligand therapy (RLT) of Lu-EB-PSMA in patients with metastatic castration-resistant prostate cancer (mCRPC). Thirty men with progressive mCRPC previously treated with taxane-based chemotherapy and second-generation androgen deprivati-on therapy were enrolled. All patients received up to three cycles of approximately 2.0 GBq (55 mCi) Lu-EB-PSMA per cycle at 8-week intervals. The primary endpoint was therapeutic safety, including the changes of hematologic status, liver function, and renal function tests; the additional primary endpoint was therapeutic efficacy, including prostate-specific antigen (PSA) response and molecular imaging response; the secondary endpoints were PSA progression-free survival (PSA-PFS) and overall survival (OS). Another endpoint was patient-reported health-related quality-of-life (HRQOL). From January 2019 to December 2021, 30, 22 and 11 patients received 1, 2 and 3 cycles of Lu-EB-PSMA RLT, respectively. During the entire follow-up period, 33.3% of patients experienced grade 3 hematological adverse events. Seventeen (56.7%) patients achieved a PSA reduction of at least 50%. The median PSA-PFS was 4.6 mo (95% CI, 2.7-6.5 mo), and the median OS was 12.6 mo (95% CI, 8.1-17.1 mo). A higher whole-body PSMA mean standardized uptake value (SUVmean) was correlated with a better PSA response; higher baseline alkaline phosphatase and larger total PSMA-positive tumor volume (PSMA-VOL) were associated with worse PSA-PFS, whereas the existence of visceral metastases and PSA at baseline were significant prognosticators of worse OS. HRQOL outcomes improved significantly after Lu-EB-PSMA RLT. RLT based on approximately 2.0 GBq of Lu-EB-PSMA for up to 3 cycles may achieve a comparable PSA response and hematological toxicity with 7.4 GBq doses of Lu-EB-PSMA for up to 4-6 cycles. Further studies with more cycles of Lu-EB-PSMA RLT are needed to evaluate the potential benefits in terms of PFS and OS.