The efficacy and safety of 177Lu-PSMA-617 in metastatic castration resistant prostate cancer (mCRPC): Single-institution, real-world data.

Abstract

e17040 Background: Lutetium Lu 177 vipivotide tetraxetan is a radiopharmaceutical that had received FDA approval in March 2022 for men with prostate-specific membrane antigen (PSMA) positive mCRPC who received taxane-based chemotherapy and an androgen receptor pathway inhibitor (ARPI). In the past year, the FDA expanded its indication to mCRPC patients who had received ARPI and were considered appropriate candidates for delaying taxane-chemotherapy. We present real-world data from a single institution using 177-Lu PSMA-617. Methods: After IRB approval, the electronic medical record (EMR) was retrospectively reviewed for patients who had received 177-Lu PSMA-617 from 2022-2025. We collected data on age, prior and subsequent lines of treatment (LOT), efficacy, progression-free survival (PFS), overall survival (OS), and toxicity profile. Results: A total of 81 patients received a median of 4 cycles of 177-Lu PSMA-617 at our institution. The median age was 75 years. The most common prior LOTs received were androgen deprivation therapy (84%), chemotherapy (82%), ARPI (72%), and radium-223 (19%). 16 (20%) patients were not exposed to any previous chemotherapy. PSA50 was achieved in 18 (23%) patients, and PSA90 in 15 (19%) patients. On further stratification, PSA50 was achieved in 4 (25%) chemo-naïve (CN) patients, and 14 (22%) chemotherapy-exposed (CE) patients. PSA90 was achieved in 7 (44%) CN patients, and 8(13%) CE patients. 22 (31%) patients had stable disease based on serum PSA, and 59 (73%) had progression of disease (POD) based on serum PSA and PSMA scan combined. The median PFS was 8 months (95% CI 6-10) in the entire population, with 9 months (95% CI 6-not reached) in CN patients, comparable to 9.3 months as per the PSMAfore trial, and 8 months (95% CI 5-13) in CE patients, comparable to the PFS of 8.7 months as per the VISION trial. The overall survival in either group was not reached (NR) (95% CI 24.1-NR). The toxicity profile was as follows: fatigue (53%), dry mouth (30%), anemia (14%), nausea/vomiting (12%). We had to interrupt treatment in 50 (62%) patients, mostly because of POD (37%), cytopenia (12%), patient preference (5%), skin infection/inflammation (2%), renal failure (2%), hepatotoxicity (1%), and muscle pain (1%). Among the most common subsequent LOT received are cabazitaxel (12%), DB-1311 (9%), immunotherapy (7%), chemotherapy (5%). 3 (3.7%) patients required hospitalization because of cytopenias requiring transfusion support. 25 (31%) patients expired as a result of POD. Conclusions: We reviewed the real-world efficacy and safety of177-Lu PSMA-617 in mCRPC at our institution. We found that chemotherapy naïve patients had a longer PFS, but the OS was not reached in either subgroup.