Dr Morris on Lutetium Lu 177 Vipivotide Tetraxetan Plus an ARPI in PSMA+ mHSPC

“The reason for the approval was that the primary end point, which is radiographic progression-free survival, was favored with the triplet therapy as opposed to the doublet therapy, and that risk reduction of progression or death was 33% in favor of the triplet.”

Michael J. Morris, MD, the prostate cancer section head of genitourinary oncology and the Steven A. Greenberg Chair in Prostate Cancer Research at Memorial Sloan Kettering Cancer Center, discussed findings from the phase 3 PSMAddition trial (NCT04720157) which supported the July 2026 FDA approval of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus an androgen receptor pathway inhibitor (ARPI) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic androgen pathway modulation–naive/sensitive prostate cancer, also known as metastatic hormone-sensitive prostate cancer (mHSPC).

Lutetium Lu 177 vipivotide tetraxetan has primarily been used in patients who developed progression on androgen deprivation therapy (ADT) and at least one ARPI, either before chemotherapy, per the phase 3 PSMAfore trial (NCT04689828), or after chemotherapy, per the phase 3 VISION trial (NCT03511664), Morris began. PSMAddition, Morris said, was the first trial of lutetium Lu 177 vipivotide tetraxetan in patients with newly diagnosed metastatic disease who were androgen pathway modulator sensitive, he noted.

The trial enrolled 1144 patients with PSMA-avid disease, identified via PSMA-PET imaging, who were being treated with standard-of-care ADT plus an ARPI, according to Morris. Patients were randomly assigned to a triplet of ADT, an ARPI, and lutetium Lu 177 vipivotide tetraxetan, or to a doublet of ADT and an ARPI alone, he said. The triplet regimen was given as 6 doses every 6 weeks, meaning the 2 study arms differed only over an initial 36-week period, he added.

The approval was supported by a 33% reduction in the risk of radiographic progression or death with the triplet regimen vs the doublet (HR, 0.67; 95% CI, 0.55-0.82) in an updated analysis, Morris said. Data also showed a positive trend toward improved overall survival with the triplet (HR, 0.80; 95% CI, 0.63-1.01), although this end point had not yet matured at the time of the analysis, he added.