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

“[These data] show using contemporary standards [and] a contemporary active control arm, that lutetium Lu 177 vipivotide tetraxetan, in addition to ADT and an ARPI, confers clinical benefit.”

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 additional data 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).

Data from the primary analysis of PSMAddition showed a radiographic progression-free survival (rPFS) hazard ratio (HR) of 0.72 (95% CI, 0.58-0.90) in favor of the investigational arm, representing a 28% relative reduction in the risk of radiographic disease progression or death with the lutetium-containing regimen, Morris began. The treatment was associated with a higher incidence of grade 3 or greater adverse effects (AEs), he noted. Despite the difference in high-grade toxicities, longitudinal quality-of-life assessments presented at the 2026 Genitourinary Cancers Symposium were similar between treatment groups, he added. AEs were primarily grade 1 or 2 and were not considered serious, consistent with the known uptake of PSMA-targeted therapy in the salivary glands, he said.

Updated data have further strengthened the efficacy signal, Morris underscored. The most recent rPFS analysis demonstrated a HR of 0.67 (95% CI, 0.55-0.82), improving on the original result, he noted. Updated overall survival data showed a HR of 0.80 (95% CI, 0.63-1.01), suggesting a favorable trend that requires additional follow-up, he said.

An important feature of the study is that it evaluated lutetium Lu 177 vipivotide tetraxetan against a contemporary treatment backbone of androgen deprivation therapy (ADT) plus an ARPI, Morris explained. Historically, chemotherapy data were generated in trials where docetaxel served as the control or foundational therapy, leaving uncertainty about the benefit of adding chemotherapy to modern hormonal therapy, he noted. This study therefore provides evidence that adding lutetium to contemporary ADT plus ARPI therapy can provide additional clinical benefit, he concluded.