Real world outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with lutetium-177-PSMA-vipivotide tetraxetan (Lu177-PVT).

Abstract

86 Background: Lu177-PVT is a novel radioligand, which was recently approved by the FDA to treat mCRPC. Real world data on its use and efficacy is limited. We aimed to build a new retrospective cohort of patients with mCRPC treated with 177Lu PSMA-617 in order to investigate clinical and pathological variables associated with treatment responses. Methods: We identified patients with a confirmed diagnosis of prostate cancer and were treated at Stanford University Medical Center with at least one dose of Lu177-PVT including trial patients. Data collection included demographic, clinicopathological and outcome variables. Statistical analysis was performed using Chi-squared and log-rank Kaplan-Meier analysis. Results: We identified 85 patients who met study criteria and were treated between March 2021 and June 2023, the median age was 66, 33% were non-white, median PSA at treatment initiation was 60, and 94% had osseous metastasis. Patients were pretreated with a median of six lines (range: 1-10) of prior therapy including local therapies; prostatectomy (28%), radiation (61%), brachytherapy (11%), taxane (78%), immunotherapy including checkpoint inhibitor and Sipuleucel-T (24%), PARP inhibitor (6%), and Radium-223 (15%). A majority of patients also received prior germline or somatic genetic testing (79%), with homologous recombination germline and somatic deficiencies present in 13% of patients. Of the identified cohort, 19 patients were still undergoing active treatment with Lu177-PVT at the time of data collection. Of the 66 patients not currently undergoing active Lu177-PVT treatment, 29 patients discontinued treatment due to progressive disease (44%) and 14 (21%) to toxicity related to 177Lu PSMA-617, completing a median of 4 cycles. 47 patients (71%) had an overall decline in their PSA from baseline, with 32 patients (49%) experiencing a decrease greater than fifty percent. Median overall survival of patients not actively receiving 177Lu PSMA-617 treatment was 366 days. Age, previous lines of therapy, and median time from diagnosis were not predictive of PSA treatment response (greater than fifty-percent reduction from baseline PSA). Conclusions: Lu177-PVT is a promising treatment for mCRPC in patients. Our results confirm ‘real-world’ activity of Lu177-PVT and align well with VISION study results, though real-world overall survival was comparatively shorter (12 months vs 15 months in VISION trial). Further investigation is warranted into predictors of response and toxicity.