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PSMAddition

[177Lu]Lu-PSMA-617 with androgen deprivation therapy plus an androgen receptor pathway inhibitor versus ADT plus ARPI in PSMA-positive metastatic androgen pathway modulator-naive or -sensitive prostate cancer

Phase 3N = 1,144NCT04720157

Population
PSMA-positive metastatic androgen pathway modulator-naive or -sensitive (metastatic hormone-sensitive) prostate cancer, treatment-naive or minimally treated; 1144 randomised (the registry record lists 1140): 50% de novo metastatic, 68% high-volume disease
Design
Randomised (1:1), open-label phase 3 superiority trial at 169 sites in 20 countries of intravenous 177Lu-PSMA-617 (7.4 GBq every 6 weeks for up to six cycles) with ADT plus ARPI, or ADT plus ARPI alone (ADT and ARPI investigator-chosen). Eligibility required one or more PSMA-positive metastatic lesion on centrally read 68Ga-PSMA-11 PET. Control-arm patients with centrally confirmed radiographic progression could cross over. The primary endpoint was radiographic progression-free survival by blinded central assessment; the paper reports the second interim analysis (data cutoff 13 January 2025).
Primary endpoint
rPFS
Arms
  • 177Lu-PSMA-617 plus ADT and ARPI (experimental, n = 572): 177Lu-PSMA-617 7.4 GBq (200 mCi) +/- 10% every 6 weeks for up to six cycles, with ADT plus ARPI
  • ADT plus ARPI (control, n = 572): ADT plus ARPI, investigator-chosen per local product labelling
People
Tagawa ST
rPFSHR 0.72 (95% CI 0.58–0.90)
Show the numbers
Results reported for PSMAddition
EndpointAnalysis177Lu-PSMA-617 plus ADT and ARPIADT plus ARPIEffect
rPFSTime from randomisation to radiographic progression or death, assessed centrally (PCWG3-modified RECIST 1.1)interimmedian follow-up 19.6 monthsTagawa 2026——HR 0.72 (95% CI 0.58–0.90)P=0.0021Second interim analysis. Radiographic progression or death occurred in 139 (24%) of 572 participants with 177Lu-PSMA-617 and 172 (30%) of 572 in the control arm; median rPFS was not reached in either arm. The figure of 19.6 months is the median rPFS follow-up time; the median time from randomisation to data cutoff was 23.6 months.
Results reported for PSMAddition
EndpointAnalysis177Lu-PSMA-617 plus ADT and ARPIADT plus ARPIEffect
rPFSTime from randomisation to radiographic progression or death, assessed centrally (PCWG3-modified RECIST 1.1)interimmedian follow-up 19.6 monthsTagawa 2026——HR 0.72 (95% CI 0.58–0.90)P=0.0021Second interim analysis. Radiographic progression or death occurred in 139 (24%) of 572 participants with 177Lu-PSMA-617 and 172 (30%) of 572 in the control arm; median rPFS was not reached in either arm. The figure of 19.6 months is the median rPFS follow-up time; the median time from randomisation to data cutoff was 23.6 months.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
rPFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
rPFS0.720.58–0.9
Primary publication: Tagawa ST, Sartor O, Piulats JM, Saad F, Fizazi K, Reid A, et al. [(177)Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial. Lancet. 2026;408(10557):793-807. PubMedDOI

Appears in

Sources

  1. Tagawa ST, Sartor O, Piulats JM, Saad F, Fizazi K, Reid A, et al. [(177)Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial. Lancet. 2026;408(10557):793-807.

    PubMedDOI