When added to the protocol-allowed standard of care (SoC) in patients with progressive, PSMA-positive metastatic castration-resistant prostate cancer, lutetium (177Lu) vipivotide tetraxetan ([177Lu]Lu-PSMA-617; 177Lu-PSMA-617) prolonged radiographic progression-free survival (rPFS) and overall survival (OS). With 177Lu-PSMA-617 with SoC therapy compared to SoC alone, a larger percentage of patients had verified a drop from baseline in prostate-specific antigen (PSA) level ≥50%. For a post hoc, exploratory study, researchers sought to assess correlations between clinical outcomes in the 177Lu-PSMA-617 group and the degree of PSA drop from baseline.
By the amount of the best PSA drop that was validated from baseline, patients in the 177Lu-PSMA-617 group were divided into 4 subgroups: no decline, ≤50% decline, > 50 – ≤90% decline, and > 90% decline (cut-off date: 27 January 2021). PSA levels were measured at the beginning of each 6-week treatment cycle and the baseline. The Kaplan-Meier technique was used to determine the median OS and rPFS. Cox proportional-hazards regression was used to determine the hazard ratios (HRs).
Prolonged rPFS and OS in the 177Lu-PSMA-617 group were linked with a greater PSA reduction from baseline. In comparison to patients with no PSA decline, those with PSA declines between >50 – ≤90% and > 90% had 80% and 96% lower risks of radiographic disease progression and 58% and 90% lower risks of death, respectively. Additionally, landmark analyses will be provided.
In the investigation, individuals with mCRPC treated with 177Lu-PSMA-617 with SoC showed a substantial correlation between the degree of PSA drop from baseline and extended rPFS and OS. It implied that in the patient population, and PSA decrease was prognostically significant for the clinical outcomes following radioligand treatment with 177Lu-PSMA-617.