225Ac-PSMA-617 Augmentation After Insufficient Response Under 177Lu-PSMA-617 Radioligand Therapy in mCRPC: Evaluation of Outcome and Safety From a Prospective Registry (REALITY Study)

• Published in: Clinical nuclear medicine 2024-12
• Main Authors: Rosar, Florian, Khreish, Fadi, Nagel, Lea Sophie, Blickle, Arne, Burgard, Caroline, Petto, Sven, Bastian, Moritz B, Speicher, Tilman, Bartholomä, Mark, Maus, Stephan, Schaefer-Schuler, Andrea, Ezziddin, Samer
• Format: Article
• Language: English
• ISSN: 0363-9762; 1536-0229; 1536-0229
• DOI: 10.1097/RLU.0000000000005640

Even though the introduction of 177Lu-PSMA-617 RLT represents a major milestone in the treatment of mCRPC, there are still patients who do not respond adequately to this therapy and for whom there are only limited options left. Augmenting 177Lu-PSMA-617 RLT with the alpha-emitter 225Ac-PSMA-617 may present an escalating treatment option to increase efficacy. In this study, we aim to evaluate outcome and safety of 225Ac-PSMA-617 augmentation to 177Lu-PSMA-617 RLT in patients who present insufficient response to monotherapy with 177Lu-PSMA-617 RLT. The study included n = 51 mCRPC patients enrolled in a prospective registry receiving 177Lu-PSMA-617 monotherapy and showing insufficient response, followed by initiation of 225Ac-PSMA-617 augmentation, with adjusted activities depending on individual patient characteristics. Biochemical response, progression-free survival, and overall survival were assessed. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE v.5.0). After initiation of 225Ac-PSMA-617 augmentation to 177Lu-PSMA-617 RLT, 24/51 patients (47.1%) exhibited partial remission, 16/51 (31.4%) stable disease, and 11/51 (21.6%) progressive disease. The median progression-free survival and overall survival rates were 6.3 months and 9.1 months, respectively. The majority of CTCAE gradings remained stable after initiating augmentation. Severe adverse events were rare, and no treatment termination due to side effects was recorded. 225Ac-PSMA-617 augmented 177Lu-PSMA-617 radioligand therapy seems to be an effective escalating treatment option in patients after failure of conventional 177Lu-PSMA-617 RLT and represents a promising approach balancing antitumor effect and tolerable side effects.