International Journal of Medical Advances and Discoveries

International Journal of Medical Advances and Discoveries | Vol. 17, No. 8, August 2026 | pp. 64–72

DOI: 10.46882/2026/IJMAD/000119

Original Research Article

Title: Efficacy of 177Lu-PSMA-617 Radioligand Therapy Combined with Enzalutamide in Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase II Trial

Names of Authors: Heinrich M. Kraemer¹, Amina J. Vance², Arthur L. Sterling¹

Authors’ Affiliations: ¹Department of Nuclear Medicine, Technical University of Munich, Munich, Germany; ²Division of Oncology, Olivia Newton-John Cancer Research Institute, Melbourne, Australia

Abstract: Radioligand therapy using Lutetium-177-PSMA-617 (177Lu-PSMA-617) has established efficacy in metastatic castration-resistant prostate cancer (mCRPC) post-chemotherapy. Preclinical models suggest that androgen receptor inhibitors can up-regulate prostate-specific membrane antigen (PSMA) expression, creating a synergistic therapeutic landscape. This open-label, randomized phase II trial investigated the clinical efficacy and safety of combining 177Lu-PSMA-617 with enzalutamide versus 177Lu-PSMA-617 monotherapy in 120 patients with progressive mCRPC. Participants were randomized 1:1 to receive either 177Lu-PSMA-617 (7.4 GBq every 6 weeks for up to 6 cycles) plus daily enzalutamide (160 mg) or 177Lu-PSMA-617 alone. The primary endpoint was a prostate-specific antigen (PSA) response rate, defined as a reduction of 50% or more from baseline (PSA50). The combination therapy cohort achieved a significantly higher PSA50 response rate compared to the monotherapy arm (78.3% [47 of 60] vs. 56.7% [34 of 60], p = 0.012). Median radiographic progression-free survival (rPFS) was substantially longer in the combination group (11.6 months vs. 7.2 months; Hazard Ratio = 0.54, 95% Confidence Interval [0.38, 0.77], p = 0.002). Grade 3 or 4 hematological toxicities, including anemia (13.3% vs. 10.0%) and thrombocytopenia (8.3% vs. 6.7%), did not differ significantly between the arms (p > 0.05). Concomitant administration of 177Lu-PSMA-617 and enzalutamide significantly enhances anti-tumor activity and delays radiographic progression in mCRPC.

Keywords: Radioligand therapy, 177Lu-PSMA-617, Enzalutamide, Castration-resistant prostate cancer, PSA response, Progression-free survival

Manuscript Timeline: Received: May 12, 2026; Revised: June 24, 2026; Accepted: July 15, 2026; Published: August 11, 2026

Citation: Kraemer, H. M., Vance, A. J., & Sterling, A. L. (2026). Efficacy of 177Lu-PSMA-617 Radioligand Therapy Combined with Enzalutamide in Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase II Trial. International Journal of Medical Advances and Discoveries, 17(8), 64–72. doi.org

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