Performance of ¹⁷⁷ Lu-PSMA-I&T for RLT in mCRPC: First prospective data of a multicenter Swiss registry study.

e17063 Background: 177 Lu-PSMA-617 has been established as a radioligand therapy (RLT) for patients with metastatic castration-resistant prostate cancer (mCRPC), demonstrating improved overall survival (OS) compared to the standard of care and a more favorable toxicity profile than chemotherapy in previously conducted prospective studies. 177 Lu-PSMA-I&T has been used as an alternative radioligand, with assumed bioequivalence for RLT in mCRPC. However, no prospective data on its safety and efficacy are currently available. Methods: Prospective, multicenter Swiss registry study (EKNZ 2021-01271) involving mCRPC patients undergoing RLT with 177 Lu-PSMA-I&T. Safety was assessed through laboratory parameters and adverse events (AEs) graded per CTCAE v5.0, evaluated before each treatment cycle and at 12 weeks after therapy completion. Efficacy was measured by PSA changes (based on PCWG3 criteria and PSA 90 , defined as a 90% PSA reduction) and imaging responses, including SPECT/CT after each cycle and CT, MRI, or PSMA PET-CT at 8–12 weeks post-RLT, with follow-ups every 6 months or as clinically indicated. Descriptive and comparative statistics, along with multivariate and Kaplan-Meier analyses, were performed to evaluate therapy safety, response, progression-free survival, and overall survival. Results: A total of 333 consecutive mCRPC patients received a median of 4 cycles of 177 Lu-PSMA-I&T (range: 1–6 cycles) over a median duration of 5.6 months (range: 0.7–11.3 months), with a cumulative activity of 24 GBq (range: 7–48 GBq). Patient characteristics included Gleason score >8 (72%), metastases in lymph nodes (71%), bones (94%), and visceral organs (26%). Most patients had prior treatment with ARSi (88%) and taxane-based chemotherapy (87%). The median follow-up was 12 months. Therapy-related adverse events (AEs) of any grade were anemia (27%), leukopenia (15%), thrombopenia (22%), neutropenia (8%), and acute kidney injury (14%). Grade 3–4 AEs were observed in 8%, 2%, 3%, 0%, and 0% of patients, respectively. The best PSA response during RLT showed a partial response (PR) in 41% and stable disease (SD) in 27%, with PSA 90 achieved in 17%. At 12 weeks post-RLT, PSA responses included PR in 26% and SD in 11%. Median overall survival (OS) was 13 months (95% CI: 11.7–14.3), PSA progression-free survival (PFS) was 4.1 months (95% CI: 3.4–4.8), and imaging PFS was 6.5 months (95% CI: 5.4–7.6). Conclusions: The first prospective multicenter registry data demonstrated that 177 Lu-PSMA-I&T therapy is safe and effective in mCRPC. When comparing our real-world data to previously reported phase III studies, the toxicity profile appears similar to that of 177 Lu-PSMA-617, with comparable treatment efficacy. Clinical trial information: EKNZ 2021-01271 .