Safety Analyses of the Phase 3 VISION Trial of [Lu]Lu-PSMA-617 in Patients with Metastatic Castration-resistant Prostate Cancer.

BACKGROUND AND OBJECTIVE

[Lu]Lu-PSMA-617 (Lu-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 Lu-PSMA-617 and the impact of longer observation time for patients receiving Lu-PSMA-617 plus SoC.

METHODS

VISION was an international, open-label study. Patients were randomised 2:1 to receive Lu-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 Lu-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 Lu-PSMA-617 remained higher in the Lu-PSMA-617 arm.

CONCLUSIONS AND CLINICAL IMPLICATIONS

Longer exposure to Lu-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 Lu-PSMA-617 in this setting and the use of up to 6 cycles of Lu-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 Lu-PSMA-617 from four to six had no additional adverse side effects.