LaVallee, Chris

88 Background: The VISION (NCT03511664) and PSMAfore (NCT04689828) clinical trials have demonstrated the effectiveness of 177 Lu-PSMA-617 in patients with mCRPC who have previously received androgen receptor pathway inhibitors (ARPIs) with or without taxane-based chemotherapy. Sipuleucel-T is used for treatment of mCRPC in routine clinical practice, particularly among community urologists; however, to date, there are no data available to understand the effectiveness of 177 Lu-PSMA-617 in patients previously treated with sipuleucel-T. Methods: This was a retrospective, observational study of adult patients with a diagnosis of mCRPC who received 177 Lu-PSMA-617 between March 23, 2022, and June 27, 2025, and had a history of treatment with sipuleucel-T. Data were obtained from the PRECISION data platform, a harmonized dataset of patients with advanced prostate cancer in the US that integrates electronic health records and claims data from community, academic, urology, and medical oncology settings. The index date was the date of 177 Lu-PSMA-617 initiation. Patient characteristics and prostate-specific antigen (PSA) response rates were evaluated descriptively. Progression-free survival (PFS), defined as the time from 177 Lu-PSMA-617 initiation to disease progression or death, was analyzed using Kaplan–Meier curves. Results: A total of 290 patients met the inclusion criteria, of whom 72% were White and 12% were Black. At index, 32% of patients were treated in urology and 68% in oncology settings. The median age was 74 years, the median baseline PSA was 35.3 ng/mL (interquartile range [IQR] 10.0–99.2 ng/mL), and 57% of patients had a Gleason score of ≥8. In addition to sipuleucel-T, prior to 177 Lu-PSMA-617, 97% of patients had received ≥1 ARPI and 79% had received ≥1 taxane. The median follow-up for this cohort was 9.4 months (IQR 5.3–17.5 months). Among 144 patients with available PSA values both before and during 177 Lu-PSMA-617 treatment (representing 50% of the cohort), PSA response rates were as follows: a ≥50% reduction in PSA from baseline (PSA50) was observed in 60%, PSA80 in 42%, and PSA90 in 33% of patients. Overall, the median PFS was 15.2 months (95% confidence interval [CI] 11.6–19.4 months). Conclusions: In this real-world analysis of patients who received 177 Lu-PSMA-617 after sipuleucel-T treatment, the median PFS was similar to that observed in clinical trials, suggesting that 177 Lu-PSMA-617 can be sequenced after sipuleucel-T treatment in appropriate patients.

78 Background: 177 Lu-PSMA-617 is currently under investigation in combination with an ARPI in those with metastatic hormone-sensitive prostate cancer (PSMAddition trial: NCT04720157). This observational study was performed to assess the effectiveness of 177 Lu-PSMA-617 in combination with an ARPI in patients with mCRPC in the real-world setting. Methods: This was a retrospective cohort study of adults with mCRPC in the PRECISION data platform, a comprehensive database of prostate cancer patients compiled from diverse clinical settings in the US. Patients who received 177 Lu-PSMA-617 during March 23, 2022–June 27, 2025 were identified, among whom two cohorts were selected for inclusion: those who had evidence of ARPI use (apalutamide, darolutamide, abiraterone, or enzalutamide) at any time during 177 Lu-PSMA-617 treatment (concomitant ARPI cohort), and those who had no other treatment for mCRPC during 177 Lu-PSMA-617 treatment (no concomitant therapy cohort). The index date was initiation of 177 Lu-PSMA-617. Patient characteristics and prostate-specific antigen (PSA) responses were evaluated descriptively. Progression-free survival (PFS), defined as the time from 177 Lu-PSMA-617 initiation to disease progression or death, was estimated using Kaplan–Meier analysis. Results: A total of 1,880 patients treated with 177 Lu-PSMA-617 were identified, 140 in the concomitant ARPI cohort and 1,740 in the no concomitant therapy cohort. The median age was 74 years. Demographic characteristics were balanced between the groups, except that median baseline PSA was lower in the concomitant ARPI cohort when compared with patients in the no concomitant therapy cohort (18 ng/mL vs. 32 ng/mL). Before 177 Lu-PSMA-617 initiation, 94.3% and 73.6% of patients in the concomitant ARPI and 80.9% and 56.7% in the no concomitant therapy cohort had received ≥1 prior ARPI and ≥1 prior taxane, respectively. PSA response rates were broadly comparable between cohorts. The median (95% confidence interval) PFS was 14.7 (11.7–21.3) months among patients in the concomitant ARPI cohort vs 12.5 (11.5–13.6) months in the no concomitant therapy cohort. Ongoing follow-up aims to evaluate the impact of combining ARPI with 177 Lu-PSMA-617 on long-term clinical outcomes, including overall survival. Conclusions: The results of this study demonstrate that 177 Lu-PSMA-617 delivers clinical benefits inpatients with mCRPC with or without ARPI; however, addition of an ARPI may potentially improve these benefits. Prospective randomized controlled studies are needed to confirm this.