177Lu-PSMA-617 vs. Androgen Receptor-Directed Therapy in the Treatment of Progressive Metastatic Castrate Resistant Prostate Cancer

Summary

The purpose of this study is to determine whether 177Lu-PSMA-617 improves the Radiographic progression-free survival (rPFS) or Overall Survival (OS) compared to a change in Androgen receptor-directed therapy (ARDT) in metastatic castrate resistant prostate cancer (mCRPC) participants that were previously treated with an alternate ARDT and not exposed to a taxane-containing regimen in the CRPC or mHSPC settings. 469 participants were randomized (235 in the 177Lu-PSMA-617 group and 234 in the ARDT group.

Timeline

Start

2021-06-15

Primary completion

2022-10-02

Completion

2026-09-30

Publications

• Fizazi K, Chi KN, Shore ND, Herrmann K, de Bono JS, Castellano D, Piulats JM, Flechon A, Wei XX, Mahammedi H, Roubaud G, Fleming M, Haas T, Ghebremariam S, Kreisl TN, Rajagopalan S, Sartor O, Morris MJ; PSMAfore Investigators. Final overall survival and safety analyses of the phase III PSMAfore trial of [177Lu]Lu-PSMA-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer. Ann Oncol. 2025 Nov;36(11):1319-1330. doi: 10.1016/j.annonc.2025.07.003. Epub 2025 Jul 17.
• Fizazi K, Morris MJ, Shore ND, Chi KN, Crosby M, de Bono JS, Herrmann K, Roubaud G, Nagarajah J, Fleming M, Lewis B, Nordquist L, Carnahan N, Ghebremariam S, Hertelendi M, Castellano D, Sartor O. Health-related quality of life, pain, and symptomatic skeletal events with [177Lu]Lu-PSMA-617 in patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): an open-label, randomised, phase 3 trial. Lancet Oncol. 2025 Jul;26(7):948-959. doi: 10.1016/S1470-2045(25)00189-5. Epub 2025 May 26.
• Morris MJ, Castellano D, Herrmann K, de Bono JS, Shore ND, Chi KN, Crosby M, Piulats JM, Flechon A, Wei XX, Mahammedi H, Roubaud G, Studentova H, Nagarajah J, Mellado B, Montesa-Pino A, Kpamegan E, Ghebremariam S, Kreisl TN, Wilke C, Lehnhoff K, Sartor O, Fizazi K; PSMAfore Investigators. 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. Lancet. 2024 Sep 28;404(10459):1227-1239. doi: 10.1016/S0140-6736(24)01653-2. Epub 2024 Sep 15.

Drugs

Indications