INTRODUCTION: To enhance the effectiveness of radioligand therapy (RLT), new prostate-specific membrane antigen (PSMA) targeting radiopharmaceuticals utilizing alternative radionuclides are under active investigation. One promising alternative to the established 177Lu is the use of 161Tb. A key advantage of 161Tb is its emission of a higher proportion of low-energy conversion and Auger electrons, which may contribute to enhanced therapeutic effectiveness. This study provides a first exploratory evaluation of the efficacy and safety of 161TbTb-PSMA-617 in patients with progression after 177LuLu-PSMA-617, aiming to generate early clinical insights. METHODS: The study included 15 patients with mCRPC, who were enrolled in the "prospective registry to assess outcome and toxicity of targeted radionuclide therapy in patients with mCRPC in clinical routine" (REALITY Study; NCT04833517). All patients had received conventional PSMA RLT using 177LuLu-PSMA-617, which resulted in initial biochemical response (PSA decline ≥50%), followed by a biochemical relapse, prompting the re-initiation of PSMA RLT using 161TbTb-PSMA-617. Patients received a median of 3 (range: 2-7) cycles with mean administered activity of 5.4 ± 1.1 GBq and mean cumulative activity of 19.2 ± 6.4 GBq 161TbTb-PSMA-617. Treatment response was assessed both biochemically by serum PSA levels and through molecular imaging by total lesion PSMA (TLP) on 68GaGa-PSMA-11 PET/CT scans. Adverse events were assessed at baseline and follow-up using the "Common Terminology Criteria for Adverse Events" (Version 5.0). RESULTS: 161TbTb-PSMA-617 RLT showed response rates of 66.7% (10/15 patients) based on biochemical assessment and 86.7% (13/15 patients) based on molecular imaging assessment. Beginning with the initiation of 161TbTb-PSMA-617 RLT, the median progression-free survival (PFS) was 6.4 months, and the median overall survival (OS) was 15.5 months. In total, 6 CTCAE grade deteriorations from grade 2 to grade 3 or from grade 3 to grade 4 were observed. No discontinuation of PSMA RLT due to adverse events was reported. CONCLUSIONS: 161TbTb-PSMA-617 RLT emerges as a promising treatment option, demonstrating encouraging response rates, preliminary clinical outcomes, and a favorable safety profile as second-line RLT in progressing patients who previously benefited from 177LuLu-PSMA-617 RLT.
Rosar et al. (Fri,) studied this question.