Kim Nguyen Chi, MD, on 177Lu-PSMA-617 vs docetaxel in mCRPC

Data from the PR.21 study presented at the 2025 European Society for Medical Oncology Congress in Berlin, Germany showed no difference in radiographic progression-free survival (rPFS) between ¹⁷⁷Lu-PSMA-617 and docetaxel in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) who progressed after an androgen receptor pathway inhibitor.

In an interview with Urology Times®, Kim Nguyen Chi, MD, FRCPC, walked through the key findings from the trial. Chi is the chief medical officer of BC Canada and a professor of medicine at the University of British Columbia in Canada.

In total, the study included 199 patients who were randomly assigned 1:1 to receive ¹⁷⁷Lu-PSMA-617 (n = 100) or to docetaxel (n = 99). The primary end point was rPFS. Crossover in the trial was permitted; in total, 38 patients in the ¹⁷⁷Lu-PSMA-617 arm crossed over to received docetaxel, and 56 patients in the docetaxel arm crossed over to received ¹⁷⁷Lu-PSMA-617.

Data showed no statistically significant difference in rPFS between the 2 arms, with a median rPFS of 8.6 months (90% CI, 7.1 to 10.6) in the ¹⁷⁷Lu-PSMA-617 arm vs 10.7 months (90% CI, 7.8 to 11.1) in the docetaxel arm (HR, 1.01; 90% CI, 0.77 to 1.31; 1-sided P = .51). This finding was consistent across baseline characteristic subgroups.

However, prostate-specific antigen (PSA) response rates were higher in ¹⁷⁷Lu-PSMA-617 arm, with a PSA decline of 50% or higher observed in 36% of patients in the ¹⁷⁷Lu-PSMA-617 arm vs 16% of patients in the docetaxel arm (P = .0015).

There was no difference observed in FACT-P total score time to deterioration metric (defined as a 10-point decline) between the 2 arms (HR, 0.93; 90% CI, 0.64 to 1.35; P = .75). Grade 3 to 4 treatment-related adverse events (TRAEs) were reported in 13% of patients in the ¹⁷⁷Lu-PSMA-617 arm vs 34% of patients in the docetaxel arm. Notably, 15 patients in the docetaxel arm discontinued treatment due to a TRAE compared with only 1 patient in the ¹⁷⁷Lu-PSMA-617 arm.

Chi also noted, “What we saw for the patients that were initially randomized to docetaxel and then crossed over, subsequently, they had a longer survival. This was hazard ratio of 1.64, so it was a substantial increase.”

DISCLOSURES: Chi noted honoraria/consulting or funding disclosures with Amgen, Astellas, AstraZeneca, Bayer, BMS, Janssen, Lily, Merck, Novartis, Pfizer, and Roche.

REFERENCE

1. Chi KN, Saad F, Ding KU, et al. A randomized phase II study of 177Lu-PSMA-617 vs docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) and PSMA-positive disease: Canadian Cancer Trials Group (CCTG) study PR.21. Presented at: 2025 European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. LBA89