Comparison of mCRPC [177Lu]Lu-PSMA-617 radioligand therapy with and without concurrent enzalutamide medication in a real-world setting
Rosar F, Khreish F, Burgard C, Fursov A, Blickle A, Bartholomä M, Maus S, Bastian MB, Speicher T, Schaefer-Schuler A, Ezziddin S (2026)
Publication Type: Journal article
Publication year: 2026
Journal
Book Volume: 53
Pages Range: 3034-3041
Journal Issue: 5
DOI: 10.1007/s00259-025-07682-5
Abstract
Purpose: Several clinical and preclinical studies showed that ARPI medication such as enzalutamide increases the expression of PSMA in mCRPC patients and may potentially act as a sensitizer for PSMA RLT. In this study we aim to provide insight into the efficacy and safety profile of concurrent treatment with [177Lu]Lu-PSMA-617 RLT and enzalutamide and draw a comparison to [177Lu]Lu-PSMA-617 alone. Methods: In total n = 63 mCRPC patients received [177Lu]Lu-PSMA-617 RLT alongside medication with enzalutamide and were compared with n = 62 mCRPC patients receiving [177Lu]Lu-PSMA-617 without any ARPI medication. All patients participated in a prospective registry (REALITY Study, NCT04833517). The patients’ biochemical response and outcome (PFS; OS) to PSMA RLT were evaluated and compared between both groups. Adverse events were assessed according to CTCAE criteria. Results: Patients treated with PSMA RLT in combination with enzalutamide achieved a significantly higher response rate (61.9% vs. 43.5%) and experienced a significantly longer PFS (6.1 months vs. 3.5 months). Statistically significant difference in OS between the groups was not reached (p = 0.097). The adverse event profiles between the treatment groups did not differ for renal toxicity, hematoxicities and xerostomia but a more frequent rate of low-grade fatigue in the enzalutamide group was observed. The combination of PSMA RLT and enzalutamide was both safe and overall well tolerated. Conclusion: The results suggest that concurrent medication of enzalutamide during PSMA RLT may enhance response and clinical outcomes, underscoring the potential of this specific combination as a promising approach in mCRPC. Future studies, ideally in prospective setting with larger patient cohorts are warranted.
Involved external institutions
Germany (DE)How to cite
APA:
Rosar, F., Khreish, F., Burgard, C., Fursov, A., Blickle, A., Bartholomä, M.,... Ezziddin, S. (2026). Comparison of mCRPC [177Lu]Lu-PSMA-617 radioligand therapy with and without concurrent enzalutamide medication in a real-world setting. European Journal of Nuclear Medicine and Molecular Imaging, 53(5), 3034-3041. https://doi.org/10.1007/s00259-025-07682-5
MLA:
Rosar, Florian, et al. "Comparison of mCRPC [177Lu]Lu-PSMA-617 radioligand therapy with and without concurrent enzalutamide medication in a real-world setting." European Journal of Nuclear Medicine and Molecular Imaging 53.5 (2026): 3034-3041.
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