BACKGROUND: In this post hoc analysis of the phase 3 VISION study of lutetium (177Lu) vipivotide tetraxetan (177Lu-PSMA-617) + standard of care (SoC) vs SoC alone in adults with progressive, prostate specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC), we assess associations of magnitude of PSA decline with time to worsening (TTW) of health-related quality of life (HRQoL) and overall response rate (ORR); and of TTW of HRQoL with radiographic progression-free survival (rPFS) and overall survival (OS).
METHODS: Associations of PSA decline with TTW of HRQoL (n = 385) or ORR (n = 319) were assessed in the 177Lu-PSMA-617 arm. Patients were grouped by magnitude of PSA decline overall or up to 12 weeks’ treatment: no decline; ≤ 50%; 51–90%; and > 90%. Worsening of HRQoL was defined as a decrease of ≥ 10 (total) or ≥ 3 (subdomains) points in FACT-P, ≥ 2 points in BPI-SF, or any decrease in EQ-5D-5L. Associations of rPFS or OS with TTW of HRQoL were carried out in the full analysis set (FAS; N = 831) using 3 Spearman’s rank methods (restricted, highest rank, and iterative multiple imputation), with and without imputation for missing OS and rPFS data.
RESULTS: In the 177Lu-PSMA-617 arm, greater PSA declines overall and up to 12 weeks’ treatment were associated with longer median TTW in FACT-P total and subdomain scores, with the largest effect in emotional wellbeing (Table). Numbers of patients with complete or partial response also increased with increasing PSA decline overall and up to 12 weeks’ treatment. Correlations of rPFS and OS with and without imputation with FACT-P, BPI-SF and EQ 5D 5L scores were positive and significant in both treatment arms, but mainly weak-to-moderate (< 0.7). In the total FAS, correlations were strongest for FACT-P emotional wellbeing (Table).
CONCLUSIONS: Greater PSA decline and increased rPFS and OS were all associated with improved HRQoL outcomes.
