{"entity":{"id":"psmaddition","kind":"trial","name":"PSMAddition","aka":[],"tldr":"PSMAddition moved the radioligand Pluvicto into the first treatment of metastatic hormone-sensitive prostate cancer, given alongside hormone therapy, and the FDA approved this use on 31 July 2026. It delayed progression on scans, but severe side effects were more common and whether it lengthens life is not yet known.","summary":"PSMAddition, trial NCT04720157 sponsored by Novartis and reported in 2025, moved Pluvicto, or 177Lu-PSMA-617, into the first-line treatment of metastatic prostate cancer, and the FDA approved this use on 31 July 2026. It randomised 1,144 men with PSMA-positive metastatic hormone-sensitive disease to the radioligand plus androgen deprivation and an androgen receptor pathway inhibitor or to standard care alone, and met its primary radiographic progression-free survival endpoint at the second interim analysis, data cut-off 13 January 2025, with a hazard ratio of 0.72 and the median not reached in either arm, while overall survival was not reported and severe adverse events were more common. OnCo links it to radioligand therapy, the CRPC term and the idea of alpha-emitting PSMA therapy at first diagnosis. Whether early radioligand use improves survival or only delays progression is the open question.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT04720157","url":"https://clinicaltrials.gov/study/NCT04720157"},{"label":"FDA approval 31 Jul 2026","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lutetium-lu-177-vipivotide-tetraxetan-androgen-receptor-pathway-inhibitor-therapy"},{"label":"Annals of Oncology LBA6 (ESMO 2025)","url":"https://www.annalsofoncology.org/article/S0923-7534(25)04871-9/fulltext"}],"tags":[],"related":[],"cancers":["prostate","prostate-mhspc"],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":["pluvicto"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["castration-resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-psmaddition-lancet-2026"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04720157","phase":"3","setting":"PSMA-positive metastatic hormone-sensitive prostate cancer: 177Lu-PSMA-617 + ADT + ARPI vs ADT + ARPI","sponsor":"Novartis","result":"rPFS HR 0.72 (95% CI 0.58 to 0.90, p=0.0021), medians not reached in either arm at the second interim analysis; overall survival not yet reported.","started":"2021-06-09","startedType":"actual","yearReported":2025,"enrolled":1144,"enrolledBasis":"registry","outcomes":[{"endpoint":"Radiographic progression-free survival","primary":true,"unit":"months","arms":[{"name":"177Lu-PSMA-617 + standard care (ARPI + ADT)","note":"Updated HR 0.67; OS HR 0.80, immature"},{"name":"Standard care"}],"hr":0.72,"ci":[0.58,0.89],"p":"0.0016","source":"https://clinicaltrials.gov/study/NCT04720157"}],"replication":"Extends VISION and PSMAfore into hormone-sensitive disease; supported the July 2026 label expansion."},"route":"/trials/psmaddition/","neighbours":{"cancer":[{"id":"prostate-mhspc","kind":"cancer","name":"Metastatic hormone-sensitive prostate cancer","route":"/cancers/prostate-mhspc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"}],"drug":[{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"term":[{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"}],"paper":[{"id":"paper-psmaddition-lancet-2026","kind":"paper","name":"[ 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","route":"/key-papers/paper-psmaddition-lancet-2026/"}],"idea":[{"id":"idea-alpha-first-mhspc","kind":"idea","name":"Alpha-emitting PSMA therapy at first metastatic diagnosis","route":"/ideas/idea-alpha-first-mhspc/"},{"id":"idea-total-body-pet-dosimetry","kind":"idea","name":"Total-body PET for personalised radioligand dosing","route":"/ideas/idea-total-body-pet-dosimetry/"}]}}