First real-world clinical experience with [Lu]Lu-PSMA-I&T in patients with metastatic castration-resistant prostate cancer beyond VISION and TheraP criteria.

Purpose: To report real-world clinical experience with [Lu]Lu-PSMA-I&T targeted radionuclide therapy (TRT) in patients with metastatic castration-resistant prostate cancer (mCRPC) in a single tertiary referral university hospital.

Methods: Patients with mCRPC who were treated with [Lu]Lu-PSMA-I&T TRT as standard of care between February 2022 and August 2023 were included in this retrospective study. Patients were treated with a maximum of six cycles with a fixed activity of 7.4 GBq/100µg [Lu]Lu-PSMA-I&T per cycle.

Results: 50 patients with mCRPC were included, of them 84% had prior therapy with two lines of taxane-based chemotherapy treated and at least one line of androgen receptor signaling inhibitor. A total of 126 cycles with a median of 2 cycles (IQR 1-6) [ Lu]Lu-PSMA-I&T were administered per patient. PSA declines of ≥ 50% and ≥ 70% were achieved in 16% and 10% of the patients, respectively. Radiological response was achieved in 11% of the patients. In total, 68 treatment-related Adverse Events (TRAEs) were observed, mainly grade 1-2 in 88% of cases. Grade 3/4 TRAEs were observed in 12% of cases. No grade 3 or higher xerostomia was reported. Median progression-free survival was 7.7 months (95% CI 4.0-11.3) and median overall survival was 8.1 months (95% CI 5.0-11.3).

Conclusion: In heavily pretreated patients with mCRPC, treatment of [Lu]Lu-PSMA-I&T TRT is well tolerated and safe, but real-world efficacy of [Lu]Lu-PSMA appears lower compared to data from recent phase-3 clinical trials using a different radioligand [Lu]Lu-PSMA-617. Further studies may show whether patients with mCRPC benefit more from [Lu]Lu-PSMA when initiated at an earlier stage of treatment.