In PSMAfore, [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolonged radiographic progression-free survival (rPFS) in taxane-naive patients with metastatic castration-resistant prostate cancer (mCRPC), with a favourable safety profile, versus a change in androgen receptor pathway inhibitor (ARPI).
We report the final overall survival (OS) analysis and updated safety data.
PSMAfore (NCT04689828) was an open-label, international, phase 3 trial. Patients with prostate-specific membrane antigen (PSMA)-positive mCRPC who had experienced disease progression once on a previous ARPI and were candidates for ARPI change were randomized 1:1 to 177Lu-PSMA-617 or ARPI change to abiraterone or enzalutamide. Crossover from ARPI change to 177Lu-PSMA-617 was allowed after centrally confirmed radiographic progression. Endpoints included rPFS (primary), OS (key secondary), and safety (secondary).
Patients were randomized to 177Lu-PSMA-617 or ARPI change (n = 234 each): 141/234 participants (60.3%) randomized to ARPI change crossed over (75.4% of those with centrally confirmed radiographic progression). The median OS was 24.48 months (95% CI 19.55-28.94) with 177Lu-PSMA-617 versus 23.13 (19.61-25.53) with ARPI change (hazard ratio [HR] 0.91 [95% CI 0.72-1.14]; p = 0.20) based on the intention-to-treat (ITT) principle; the crossover-adjusted OS HR by inverse probability of censoring weighting modelling was 0.59 (95% CI 0.38-0.91). For 177Lu-PSMA-617 versus ARPI change, exposure-adjusted incidences of grade ≥ 3 and serious treatment-emergent adverse events were 60.8 versus 85.1 and 32.5 versus 49.9 per 100 patient-treatment years, respectively. Dry mouth occurred in 135/227 participants (59.5%; 2/227 grade ≥ 3) and anaemia in 62/227 (27.3%; 14/227 grade ≥ 3) in the 177Lu-PSMA-617 arm.
OS analyses did not show a statistically significant difference between the 177Lu-PSMA-617 and ARPI arms based on the ITT principle; results were likely confounded by the high rate of crossover. The safety profile of 177Lu-PSMA-617 was favourable with no new safety signals identified.
Annals of oncology : official journal of the European Society for Medical Oncology. 2025 Jul 16 [Epub ahead of print]
K Fizazi, K N Chi, N D Shore, K Herrmann, J S de Bono, D Castellano, J M Piulats, A Fléchon, X X Wei, H Mahammedi, G Roubaud, M Fleming, T Haas, S Ghebremariam, T N Kreisl, S Rajagopalan, O Sartor, M J Morris, PSMAfore Investigators
Institut Gustave Roussy and Centre Oscar Lambret, Université Paris-Saclay, Villejuif, France. Electronic address: ., BC Cancer, Vancouver, BC, Canada., START Carolinas Research Center, AUC Urology Specialists, Myrtle Beach, SC, USA., Department of Nuclear Medicine, University of Duisburg-Essen, German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany and National Center for Tumor Diseases (NCT), NCT West, Germany., The Institute of Cancer Research and The Royal Marsden Hospital, London, UK., Medical Oncology Department, Hospital Universitario 12 de Octubre, I+12 Research Institute, Madrid, Spain., Catalan Institute of Oncology, Barcelona, Spain., Centre Léon-Bérard, Lyon, France., Dana-Farber Cancer Institute, Boston, MA, USA., Centre Jean Perrin, Clermont-Ferrand, France., Institut Bergonié, Bordeaux, France., Virginia Oncology Associates, Norfolk, VA, USA., Novartis Pharma AG, Basel, Switzerland., Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA., Tulane University Medical School, New Orleans, LA, USA., Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.