Second interim analysis results from the phase 3 PSMAddition trial show adding the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy [177Lu] Lu-PSMA-617 to standard androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) significantly improved radiographic progression-free survival (rPFS) among patients with metastatic hormone-sensitive prostate cancer. 

These findings were presented by Scott Tagawa, MD, Weill Cornell Medicine, New York, New York, at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany. 

The PSMAddition trial is the first phase 3 trial of radioligand therapy in metastatic hormone-sensitive prostate cancer. The trial enrolled 1144 treatment-naïve or minimally treated (≤ 45 days) patients with PSMA-positive disease. Patients were randomized 1:1 to receive either 7.4 GBq of 177Lu-PSMA-617 once every 6 weeks for up to 6 cycles plus ADT and an ARPI (n = 572) or ADT plus an ARPI alone (n = 572). Randomization was stratified by disease volume, age (≥70 or <70 years), and whether primary tumor treatment was previously administered or planned. Crossover to the 177Lu-PSMA-617 arm was permitted if patients experienced centrally confirmed radiographic progression. 

The primary trial end point was rPFS. Key secondary end points included overall survival (OS), objective response rate (ORR), safety, and quality of life. 

At a median follow-up of 23.6 months, rPFS events occurred in 24.3% of patients in the 177Lu-PSMA-617 arm and 30.1% of patients in the control arm. Median rPFS was not reached in the 177Lu-PSMA-617 arm and was 29.7 months in the control arm (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.58 to 0.90; P = .002). OS events occurred in 14.9% of patients and 17.3% of patients and the ORR was 85.3% and 80.8%, respectively. 

Grade ≥3 adverse events occurred in 50.7% of patients in the 177Lu-PSMA-617 arm and 43% of patients in the control arm and most frequently included cytopenias. Serious adverse events occurred in 31.9% and 28.7% of patients, respectively. No meaningful difference in time to worsening quality of life was observed between treatment arms.

Source: 

Tagawa S, Sator O, Piulats JM, et al. Phase 3 trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA6