Safety Analyses of the Phase 3 VISION Trial of [177Lu]Lu-PSMA-617 in Patients with Metastatic Castration-resistant Prostate Cancer.
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ICR Authors
Authors
Chi, KN
Armstrong, AJ
Krause, BJ
Herrmann, K
Rahbar, K
de Bono, JS
Adra, N
Garje, R
Michalski, JM
Kempel, MM
Fizazi, K
Morris, MJ
Sartor, O
Brackman, M
DeSilvio, M
Wilke, C
Holder, G
Tagawa, ST
Armstrong, AJ
Krause, BJ
Herrmann, K
Rahbar, K
de Bono, JS
Adra, N
Garje, R
Michalski, JM
Kempel, MM
Fizazi, K
Morris, MJ
Sartor, O
Brackman, M
DeSilvio, M
Wilke, C
Holder, G
Tagawa, ST
Document Type
Journal Article
Date
2024-04-01
Date Accepted
2023-12-11
Date Available
2024-06-25T12:17:54Z
Abstract
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. METHODS: 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. KEY FINDINGS AND LIMITATIONS: 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. CONCLUSIONS AND CLINICAL IMPLICATIONS: Longer exposure to 177Lu-PSMA-617 plus SoC was not associated with a higher toxicity risk, and the extended time for safety observation could account for the higher TEAE incidence in comparison to SoC alone. The findings support a favourable benefit-risk profile for 6 cycles of 177Lu-PSMA-617 in this setting and the use of up to 6 cycles of 177Lu-PSMA-617 in patients who are clinically benefiting from and tolerating this therapy. PATIENT SUMMARY: For patients with metastatic prostate cancer no longer responding to hormone therapy, an increase in the number of cycles of treatment with a radioactive compound called 177Lu-PSMA-617 from four to six had no additional adverse side effects.
Citation
European Urology, 2024, 85 (4), pp. 382 - 391
Source Title
European Urology
Publisher
ELSEVIER
ISSN
0302-2838
eISSN
1873-7560
1873-7560
1873-7560
Collections
Research Team
PrCa Targeted Therapy