Clinical outcomes of lutetium-177-vipivotide tetraxetan in men with metastatic castration-resistant prostate cancer at a single academic center.

84 Background: Lutetium-177-vipivotide tetraxetan ( 177 Lu) was approved in 2022 for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with prior androgen receptor signaling inhibition (ARSI) and a taxane. The impact of 177 Lu in a non-trial setting is limited. Methods: We retrospectively reviewed records of mCRPC pts who received ≥1 dose of 177 Lu at The Ohio State University from 3/2022-3/2024. Demographics, tumor histology, metastasis sites (mets), treatment (Tx) history, standardized uptake value max (SUVm), and prostate-specific antigen (PSA), at baseline (BL) and post-Tx were collected. SUVm was defined as the highest SUV from a single lesion. Outcomes were PSA response, PSA50, radiographic progression-free (rPFS) by PCWG3, and overall survival (OS). Descriptive statistics, Mann-Whitney, Chi-square, and Cox regression model were used to assess impact. Results: A total of 152 pts were included with a median follow-up of 9 months (0.1-23 m). The median age was 70 years (46-92 y), with 39% having de novo metastatic disease, and 61% had Gleason grade group ≥4. The common mets were bone (91%), lymph node (68%), and visceral (34% with 17% liver and 8% lung). The majority received prior taxanes and ARSI, and 20% radium-223. The median lines of prior Tx was 5.The median BL PSA was 56.3 ng/mL, and the median BL SUVm was 30.4. Post-Tx, 64% showed a PSA response, and 46% achieved PSA50. Among the pts with available imaging, 17% had partial response, 12% stable disease, and 48% disease progression.Tx was discontinued in 62% for:radiographic progression (66%), PSA-only progression (7%), clinical decline (24%), and toxicity (3%). At the data cutoff, mortality was 50%. Median PFS and OS was 6.7 m, and 12.2 m respectively. BL SUVm was associated with improved PSA50 (p=0.01), rPFS (p<0.01), and OS (p=0.01), and liver mets associated with worse OS (p<0.01). Conclusions: In this retrospective study of 177 Lu, we see similar PSA and PSA50 responses to reported trials. However, PFS was shorter, and mortality was higher, likely related to the use of 177 Lu in heavily treated pts with few remaining options. Optimizing biomarkers to predict Tx benefit and resistance are needed.