Published data show rPFS benefit with lutetium Lu 177 vipivotide tetraxetan in mHSPC

Results from the phase 3 PSMAddition trial (NCT04720157) have been published in The Lancet, showing that the addition of lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617; Pluvicto) to androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) significantly extended radiographic progression-free survival (rPFS) in patients with prostate-specific membrane antigen (PSMA)-positive metastatic androgen pathway modulation-naïve or-sensitive (mAPMN/S) prostate cancer, previously referred to as metastatic hormone-sensitive prostate cancer (mHSPC).¹

The results were initially presented at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany. Findings from the study led to FDA approval of lutetium Lu 177 vipivotide tetraxetan for PSMA-positive mAPMN/S in late July 2026.

“About 9 out of 10 patients with metastatic prostate cancer have tumors that are positive for PSMA,” said lead author Scott T. Tagawa, MD, MS, FACP, FASCO, director of the Genitourinary Oncology Program at NewYork-Presbyterian/Weill Cornell Medical Center, in a news release on the study.² “Now, we have a new therapy that, when added to the backbone therapy, extended radiographic progression-free survival for almost all patients with metastatic prostate cancer.”

About the PSMAddition study

PSMAddition is a phase 3, open-label, randomized trial that enrolled 1144 patients across 169 clinical trial sites in 20 countries. Across the study cohort, 50% of patients had de novo metastatic APMN/S prostate cancer and 68% had high-volume disease. The median age was 68 years (IQR, 62 to 73).

Participants in the study were randomly assigned 1:1 to receive intravenous lutetium Lu 177 vipivotide tetraxetan plus ADT and an ARPI (n = 572) or to ADT plus an ARPI alone (n = 572). The primary end point was rPFS, with overall survival (OS) as the key secondary end point.

The trial met its primary end point, demonstrating a 28% reduction in the relative risk of radiographic progression or death with lutetium Lu 177 vipivotide tetraxetan plus ADT and an ARPI compared with ADT and an ARPI alone (HR, .72; 95% CI, 0.58 to 0.90; P = .0021). At the time of data report, 24% of patients in the treatment arm vs 30% in the control arm had experienced an rPFS event. The median rPFS had not been reached in either arm.

According to the authors, the rPFS benefit was generally consistent across subgroup analyses, including high- vs low-volume disease and de novo vs recurrent disease.

There was no significant difference in OS between the 2 treatment arms (HR, 0.84; 95% CI, 0.63 to 1.13; P = .13), though the data were immature at the time of report. The median OS had not been reached in either arm.

Novartis announced in a recent news release that a subsequent updated analysis of the data showed a 33% reduction in the risk of progression or death with lutetium Lu 177 vipivotide tetraxetan (HR, 0.67; 95% CI, 0.55 to 0.82) with a positive trend in OS (HR, 0.80; 95% CI, 0.63 to 1.01).³

The lutetium Lu 177 vipivotide tetraxetan arm also demonstrated benefit in the time to prostate-specific antigen progression (HR, 0.42; 95% CI, 0.30 to 0.59) and time to metastatic androgen pathway modulator-resistant (previously metastatic castration-resistant) prostate cancer (HR, 0.70; 95% CI, 0.58 to 0.84). The objective response rate was 85% (95% CI, 79.9 to 89.6) in the lutetium Lu 177 vipivotide tetraxetan arm vs 81% (95% CI, 74.8 to 85.8) in the control arm. Complete responses were reported in 57% and 42% of patients, respectively.

Adverse events (AEs) were reported in 98% of patients in the lutetium Lu 177 vipivotide tetraxetan arm vs 97% of patients in the control arm. Grade 3 or higher AEs occurred in 51% and 43% of patients, respectively. The most common AEs reported in the lutetium Lu 177 vipivotide tetraxetan arm were dry mouth (46%), fatigue (35%), nausea (34%), hot flush (29%), and anemia (27%). AEs led to lutetium Lu 177 vipivotide tetraxetan discontinuation, dose reduction, or dose delay in 45 (8%), 22 (4%), and 68 (12%) patients, respectively, in the treatment arm.

The PSMAddition trial is ongoing, with final completion expected in 2027.⁴

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