Scott Tagawa, MD, outlines key findings from the phase 3 PSMAddition trial

Data from the phase 3 PSMAddition trial (NCT04720157) suggest a potential role to move ¹⁷⁷Lu-PSMA-617 into an earlier disease setting.

The findings, presented at the 2025 European Society for Medical Oncology Congress in Berlin, Germany, showed that ¹⁷⁷Lu-PSMA-617 combined with androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) significantly improved radiographic progression-free survival (rPFS) in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC).

In an interview with Urology Times®, Scott T. Tagawa, MD, MS, FACP, FASCO, outlined the key findings from the study. Tagawa is a professor of medicine and urology at Weill Cornell Medicine in New York, New York.

In total, the trial randomly assigned 1144 patients 1:1 to receive ¹⁷⁷Lu-PSMA-617 (7.4 GBq q6w, 6 cycles) plus ADT and ARPI (of physician choice) or standard of care with ADT + ARPI alone. Baseline characteristics were well-balanced between both arms, as well as physician choice of ARPI.

Overall, the study reported a 28% improvement in the risk of radiographic progression or death with the addition of ¹⁷⁷Lu-PSMA-617 (HR, 0.72; 95% CI, 0.58 to 0.90; P = .002). At a median follow-up of 23.6 months, the median rPFS had not been reached in either arm. The benefit in rPFS was observed across all subgroups assessed.

Although overall survival data were immature at the time of data report, Tagawa pointed to a hazard ratio of 0.84 in favor of the ¹⁷⁷Lu-PSMA-617 arm, but confidence intervals that cross 1 (95% CI, 0.63 to 1.13; P = .125) during the presentation. Several other secondary efficacy end points–PSA end points, time to SSEs–also favored the ¹⁷⁷Lu-PSMA-617 arm.

However, Tagawa noted that toxicity was increased in the triplet arm, with grade 3 or higher adverse events (AEs) reported in 50.7% of patients in the ¹⁷⁷Lu-PSMA-617 arm vs 43% of patients in the standard of care arm. Serious AEs occurred in 31.9% and 28.7% of patients, respectively.

REFERENCE

1. Tagawa ST, Sartor O, Piulats JM, et al. Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Presented at: 2025 European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. LBA6