A Single-Arm, Low-Dose, Prospective Study of 177Lu-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 177Lu-EB-prostate-specific membrane antigen (PSMA) in patients with metastatic castration-resistant prostate cancer. Methods: Thirty men with progressive metastatic castration-resistant prostate cancer previously treated with taxane-based chemotherapy and second-generation androgen deprivation therapy were enrolled. All patients received up to 3 cycles of approximately 2.0 GBq (55 mCi) of 177Lu-EB-PSMA per cycle at 8-wk intervals. The primary endpoint was therapeutic safety, including changes in hematologic status, liver function, and renal function. An additional primary endpoint was therapeutic efficacy, including prostate-specific antigen (PSA) response and molecular imaging response. The secondary endpoints were PSA progression-free survival (PFS) and overall survival (OS). Another endpoint was patient-reported health-related quality of life. Results: From January 2019 to December 2021, 30, 22, and 11 patients received 1, 2, or 3 cycles of 177Lu-EB-PSMA RLT, respectively. During the entire follow-up period, 33.3% of patients experienced grade 3 hematologic 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 SUVmean correlated with a better PSA response, higher baseline alkaline phosphatase and larger total PSMA-positive tumor volume were associated with worse PSA PFS, and the existence of visceral metastases and higher PSA value at baseline were significant prognosticators of worse OS. Health-related quality-of-life outcomes improved significantly after 177Lu-EB-PSMA RLT. Conclusion: RLT based on approximately 2.0 GBq of 177Lu-EB-PSMA for up to 3 cycles may achieve a PSA response and hematologic toxicity comparable to those from 7.4-GBq doses of 177Lu-PSMA-617 for up to 4-6 cycles. Further studies with more cycles of 177Lu-EB-PSMA RLT are needed to evaluate the potential benefits in terms of PFS and OS.