Safety Analyses of the Phase 3 VISION Trial of 177LuLu-PSMA-617 in Patients with Metastatic Castration-resistant Prostate Cancer

• Published in: European urology 2024-04, Vol.85 (4), p.382
• Main Authors: Chi, Kim N, Armstrong, Andrew J, Krause, Bernd J, Herrmann, Ken, Rahbar, Kambiz, de Bono, Johann S, Adra, Nabil, Garje, Rohan, Michalski, Jeff M, Kempel, Mette M, Fizazi, Karim, Morris, Michael J, Sartor, Oliver, Brackman, Marcia, DeSilvio, Michelle, Wilke, Celine, Holder, Geoffrey, Tagawa, Scott T
• Format: Article
• Language: English
• ISSN: 1873-7560; 1873-7560
• DOI: 10.1016/j.eururo.2023.12.004

[177Lu]Lu-PSMA-617 (177Lu-PSMA-617) plus the standard of care (SoC) significantly improved overall survival and radiographic progression-free survival versus SoC alone in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer in the VISION trial. We evaluated the safety of additional cycles of 177Lu-PSMA-617 and the impact of longer observation time for patients receiving 177Lu-PSMA-617 plus SoC.BACKGROUND AND OBJECTIVE[177Lu]Lu-PSMA-617 (177Lu-PSMA-617) plus the standard of care (SoC) significantly improved overall survival and radiographic progression-free survival versus SoC alone in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer in the VISION trial. We evaluated the safety of additional cycles of 177Lu-PSMA-617 and the impact of longer observation time for patients receiving 177Lu-PSMA-617 plus SoC.VISION was an international, open-label study. Patients were randomised 2:1 to receive 177Lu-PSMA-617 plus SoC or SoC alone. The incidence of treatment-emergent adverse events (TEAEs) was assessed in prespecified subgroups of patients who received ≤4 cycles versus 5-6 cycles of treatment and during each cycle of treatment. The TEAE incidence was also adjusted for treatment exposure to calculate the incidence per 100 patient-treatment years of observation. This analysis was performed for the first occurrence of TEAEs.METHODSVISION was an international, open-label study. Patients were randomised 2:1 to receive 177Lu-PSMA-617 plus SoC or SoC alone. The incidence of treatment-emergent adverse events (TEAEs) was assessed in prespecified subgroups of patients who received ≤4 cycles versus 5-6 cycles of treatment and during each cycle of treatment. The TEAE incidence was also adjusted for treatment exposure to calculate the incidence per 100 patient-treatment years of observation. This analysis was performed for the first occurrence of TEAEs.The any-grade TEAE incidence was similar in cycles 1-4 and cycles 5-6. TEAE frequency was similar across all cycles of 177Lu-PSMA-617 treatment. No additional safety concerns were reported for patients who received >4 cycles. The exposure-adjusted safety analysis revealed that the overall TEAE incidence was similar between arms, but distinct trends for different TEAE types were noted and the incidence of events associated with 177Lu-PSMA-617 remained higher in the 177Lu-PSMA-617 arm.KEY FINDINGS AND LIMITA