Safety and survival outcomes in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with lutetium-177–prostate-specific membrane antigen (177Lu-PSMA) after radium-223 (223Ra) : Interim analysis of the RALU study

5040 Background: 223Ra and 177Lu-PSMA both prolong overall survival (OS) in different mCRPC settings. Previous data from the observational REASSURE (Sartor O, et al. 2021) and WARMTH (Ahmadzadehfar H, et al. 2021) studies suggested the feasibility of sequencing 223Ra and 177Lu-PSMA therapies. Here we used data from the observational, retrospective RALU study to further examine the safety and clinical outcomes of sequential 223Ra/177Lu-PSMA therapy in pts with mCRPC. Methods: This interim analysis investigated the baseline characteristics, safety (primary endpoint) and OS (secondary endpoint) in pts who received 177Lu-PSMA after 223Ra using retrospective data collected in German centers. Results: Data from 49 pts were available for this interim analysis. At baseline, before the start of 177Lu-PSMA, 73% of pts were Eastern Cooperative Oncology Group performance status (ECOG PS) 1 and 27% ECOG PS 2. Visceral metastases were present in 31% of pts. Median prostate-specific antigen (PSA) and alkaline phosphatase (ALP) were 287 ng/ml and 142 U/L, respectively (Table). 70% of pts received ≥4 life-prolonging therapies prior to 177Lu-PSMA, with abiraterone acetate (80%), enzalutamide (67%) and docetaxel (92%) being the most frequently used. 74% of pts received ≥5 223Ra injections. Pts received either PSMA-617 (67%) or PSMA I&T (33%): 65% of pts received 1–4 cycles and 33% received 5–6 cycles. Median duration of 177Lu-PSMA therapy was 4.9 months (m) (0–57.1). Median time from the last 223Ra dose to first 177Lu-PSMA dose was 9.3 m (0.9–41.9). Any grade treatment-emergent adverse events (TEAEs) from the start of 177Lu-PSMA therapy to 30 days of follow-up occurred in 91.8% of pts, and serious TEAEs in 20% of pts. Grade 3-4 hematologic laboratory abnormalities up to 90 days post-177Lu-PSMA occurred in 34.7% of pts for anemia, 12.8% for thrombocytopenia and 2.0% for neutropenia. No grade 5 toxicities occurred. 39% of pts had ≥30% decline in PSA during 177Lu-PSMA treatment. Median OS was 12.6 m (95% CI 8.8–16.1) from the start of 177Lu-PSMA therapy. Conclusions: In this real-world retrospective analysis of selected pts with advanced mCRPC, the 223Ra/177Lu-PSMA treatment sequence was clinically feasible and well tolerated. [Table: see text]