177Lu-Prostate-Specific Membrane Antigen Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer and Prior 223Ra (RALU Study)

Abstract

²²³Ra-dichloride (²²³Ra) and ¹⁷⁷Lu-prostate-specific membrane antigen (PSMA) are approved treatments for metastatic castration-resistant prostate cancer (mCRPC). The safety and effectiveness of sequential use of ²²³Ra and ¹⁷⁷Lu-PSMA in patients with mCRPC are not well described. This study aimed to evaluate ¹⁷⁷Lu-PSMA safety and efficacy in patients with mCRPC previously treated with ²²³Ra. Methods: The radium→lutetium (RALU) study was a multicenter, retrospective, medical chart review. Participants had received at least 1 ²²³Ra dose and, in any subsequent therapy line, at least 1 ¹⁷⁷Lu-PSMA dose. Primary endpoints included the incidence of adverse events (AEs), serious AEs, grade 3-4 hematologic AEs, and abnormal laboratory values. Secondary endpoints included overall survival, time to next treatment/death, and change from baseline in serum prostate-specific antigen and alkaline phosphatase levels. Results: Data were from 133 patients. Before ¹⁷⁷Lu-PSMA therapy, 56% (75/133) of patients received at least 4 life-prolonging therapies; all patients received ²²³Ra (73% received 5-6 injections). Overall, 27% (36/133) of patients received at least 5 ¹⁷⁷Lu-PSMA infusions. Any-grade treatment-emergent AEs were reported in 79% (105/133) of patients and serious AEs in 30% (40/133). The most frequent grade 3-4 laboratory abnormalities were anemia (30%, 40/133) and thrombocytopenia (13%, 17/133). Median overall survival was 13.2 mo (95% CI, 10.5-15.6 mo) from the start of ¹⁷⁷Lu-PSMA. Conclusion: In this real-world setting, ²²³Ra followed by ¹⁷⁷Lu-PSMA therapy in heavily pretreated patients with mCRPC was clinically feasible, with no indication of impairment of ¹⁷⁷Lu-PSMA safety or effectiveness.

Keywords: 177Lu-PSMA; 223Ra; metastatic castration-resistant prostate cancer; real-world practice; targeted α-therapy.