Dr Tagawa on the PSMAddition Trial of Lutetium Lu 177 Vipivotide Tetraxetan Plus ARPI and ADT in PSMA+ mHSPC

“This [study] took the backbone [of ARPI and ADT], which hopefully [most] patients are getting, and [examined it] with or without up to 6 cycles of lutetium Lu 177 vipivotide tetraxetan.”

Scott T. Tagawa, MD, MS, FACP, FASCO, a professor of medicine and urology at Weill Cornell Medicine and an attending physician at NewYork-Presbyterian – Weill Cornell Medical Center, outlined the design of the phase 3 PSMAddition trial (NCT04720157).

PSMAddition evaluated lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus an androgen receptor pathway inhibitor (ARPI) and androgen deprivation therapy (ADT) vs ARPI plus ADT alone for the treatment of patients with prostate specific-membrane antigen (PSMA)–positive metastatic hormone-sensitive prostate cancer (mHSPC). Tagawa noted that the regimen being examined in the study is aiming to build on the effective backbone of ARPI in combination with ADT, which a vast majority of patients in this disease setting are already being treated with. Patients in the investigational arm received up to 6 cycles of lutetium Lu 177 vipivotide tetraxetan at 7.4 GBq every 6 weeks, he explained.

The primary end point of the study was radiographic progression-free survival (rPFS), Tagawa noted. Patients were required to have metastatic disease per CT scan, bone scan, or MRI, he added. Other key inclusion criteria included having an ECOG performance status of 0 to 2 and adequate organ function, he said.

Findings from the study presented during the 2025 ESMO Congress revealed that patients who received lutetium Lu 177 vipivotide tetraxetan plus an ARPI and ADT (n = 572) achieved a median rPFS that was not reached (NR; 95% CI, not evaluable [NE]-NE) compared with NR (95% CI, 29.7-NE) patients treated with an ARPI and ADT alone (HR, 0.72; 95% CI, 0.58-0.90; P = .002), Tagawa said. These findings indicated a 28% reduction in the risk of death or radiographic disease progression with the combination vs the control arm, Tagawa said in conclusion.