Outcome of Subsequent Therapies After 177Lu‐Vipivotide Tetraxetan for Metastatic Castrate‐Resistant Prostate Cancer: A Tertiary Cancer Center Experience

ABSTRACT Background 177 Lu‐vipivotide tetraxetan ( 177 Lu‐PSMA‐617, LuPSMA) improves overall survival in patients with metastatic castration‐resistant prostate cancer (mCRPC) after at least one taxane chemotherapy and androgen receptor pathway inhibitor. There are limited data on the clinical course and outcomes of patients with mCRPC after receipt of LuPSMA. Methods We queried an IRB‐approved prospectively maintained registry of all patients with mCRPC who received standard‐of‐care LuPSMA at our institution between June 2022 and January 2024. Clinical data about LuPSMA and subsequent therapies were extracted from the electronic medical record, including the type and number of subsequent systemic therapies, reason for treatment cessation, hematologic toxicity and supportive treatment, and PSA50 response to subsequent therapy (defined as a ≥ 50% decrease in PSA). Results A total of 146 patients were evaluated; mean age 72 (range 52–87), observed median follow‐up 5.9 months (range 0.51–18.7). Forty‐four received systemic treatment after LuPSMA. The most common subsequent treatment after LuPSMA was chemotherapy ( n = 27), primarily cabazitaxel ± carboplatin/cisplatin ( n = 23), and the median number of cycles received was 4 (range 1–7). In 35/44 men with available hematologic toxicity data, 13 developed grade ≥ 3 anemia, 7 had ≥ grade 3 thrombocytopenia, and 16 received hematologic support. PSA50 to post‐LuPSMA treatment occurred in 10/36 (28%) evaluable patients. Median overall survival from subsequent systemic therapy was 7.6 months (95% CI 5.81–NR). Conclusions 30% of patients receiving standard‐of‐care LuPSMA received subsequent therapy, mostly cabazitaxel‐containing regimens. Post‐LuPSMA treatment appeared tolerable and was associated with a PSA50 response rate of 28%. These outcomes may be biased by limited standard‐of‐care life‐prolonging treatment options at the time of LuPSMA FDA approval, but it also highlights the continued need to develop novel therapeutic strategies for mCRPC post‐LuPSMA.