Final Data From Phase 3 PSMAfore Trial About 177Lu-PSMA-617 (Pluvicto)

The PSMAfore trial, a phase 3 study, compared 177Lu-PSMA-617 (a targeted radiation therapy) to a switch in androgen receptor pathway inhibitor (ARPI, either abiraterone or enzalutamide) in 468 men with metastatic castration-resistant prostate cancer (mCRPC) who had progressed on one prior ARPI and had not received taxane chemotherapy.

The trial, conducted across 74 global sites, allowed patients in the ARPI group to cross over to 177Lu-PSMA-617 after confirmed disease progression. Published in Annals of Oncology in July 2025, the study reports final overall survival (OS) and updated safety results.

Study Setup:

  • 468 patients split evenly: 234 received 177Lu-PSMA-617 (7.4 GBq every 6 weeks for 6 cycles), 234 switched to a different ARPI.
  • 60.3% (141/234) of ARPI patients crossed over to 177Lu-PSMA-617 after progression (75.4% of those with confirmed progression).

Survival Outcomes:

  • Radiographic Progression-Free Survival (rPFS) (primary endpoint, previously reported):
    • 59% lower risk of progression with 177Lu-PSMA-617 (HR 0.41, 95% CI 0.29–0.56, p<0.0001).

Overall Survival (OS) (key secondary endpoint):

  • Median OS: 24.48 months for 177Lu-PSMA-617 vs. 23.13 months for ARPI (HR 0.91, 95% CI 0.72–1.14, p=0.20).
  • No significant difference, likely due to crossover.
  • Adjusted for crossover: HR 0.59 (95% CI 0.38–0.91), suggesting a potential OS benefit.

Other Benefits:

  • Higher objective response rate: 50.7% for 177Lu-PSMA-617 vs. 14.9% for ARPI.
  • Improved quality of life, with delayed pain and functional decline.

Adverse Events (per 100 patient-treatment years):

  • Grade ≥3 events: 60.8 for 177Lu-PSMA-617vs. 85.1 for ARPI.
  • Serious events: 32.5 vs. 49.9.

Common side effects with 177Lu-PSMA-617:

  • Dry mouth: 59.5% (2/227 severe).
  • Anemia: 27.3% (14/227 severe).

Discontinuation due to side effects:

  • 5.7% for 177Lu-PSMA-617 vs. 5.2% for ARPI.
  • No new safety concerns.

In a nurshell, [177Lu]Lu-PSMA-617 significantly delays disease progression and shows a favorable safety profile compared to switching ARPIs. While OS did not differ significantly due to crossover, adjusted analyses suggest a survival benefit. These results, combined with better response rates and quality of life, support [177Lu]Lu-PSMA-617 as a valuable treatment for taxane-naive mCRPC patients.

Source.