{"entity":{"id":"psmafore","kind":"trial","name":"PSMAfore","aka":[],"tldr":"PSMAfore moved Pluvicto before chemotherapy in prostate cancer.","summary":"PSMAfore, trial NCT04689828 sponsored by Novartis and published in the Lancet in 2024, moved Pluvicto, or 177Lu-PSMA-617, before chemotherapy in PSMA-positive metastatic castration-resistant prostate cancer after one androgen receptor pathway inhibitor. It randomised 468 taxane-naive men to the radioligand or a switch of androgen receptor pathway inhibitor, met its primary radiographic progression-free survival endpoint with a large effect, and overall survival was confounded by crossover of most control patients, with crossover-adjusted analyses favouring the radioligand; approval in the pre-chemotherapy setting followed in 2025. Whether earlier use improves survival, not just progression, is the open question.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT04689828","url":"https://clinicaltrials.gov/study/NCT04689828"}],"tags":[],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["pluvicto"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["oliver-sartor","michael-morris"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04689828","phase":"3","setting":"PSMA+ mCRPC after one ARPI, taxane-naive: 177Lu-PSMA-617 vs ARPI switch","sponsor":"Novartis","result":"rPFS HR 0.41.","yearReported":2023,"enrolled":469,"enrolledBasis":"registry","outcomes":[{"endpoint":"Radiographic progression-free survival","primary":true,"unit":"months","arms":[{"name":"177Lu-PSMA-617","n":234,"value":12},{"name":"ARPI switch","n":234,"value":5.6}],"hr":0.41,"ci":[0.29,0.56],"p":"<0.0001","source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01653-2/fulltext"},{"endpoint":"Overall survival (crossover-adjusted)","unit":"months","arms":[{"name":"177Lu-PSMA-617","note":"Unadjusted OS HR 0.98 with 84% crossover from control"},{"name":"ARPI switch"}],"hr":0.59,"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01653-2/fulltext"}],"replication":"Confirms VISION in the pre-chemotherapy line; SPLASH (177Lu-PSMA-I&T) showed a smaller rPFS effect and no OS benefit, so agent and setting details matter."},"route":"/trials/psmafore/","neighbours":{"isotope":[{"id":"lu-177","kind":"isotope","name":"Lutetium-177","route":"/isotopes/lu-177/"}],"indication":[{"id":"prostate-mcrpc","kind":"indication","name":"Metastatic castration-resistant prostate cancer","route":"/indications/prostate-mcrpc/"},{"id":"prostate","kind":"indication","name":"Prostate cancer","route":"/indications/prostate/"}],"drug":[{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"}],"person":[{"id":"oliver-sartor","kind":"person","name":"A. Oliver Sartor","route":"/people/oliver-sartor/"},{"id":"michael-morris","kind":"person","name":"Michael J. Morris","route":"/people/michael-morris/"}],"term":[{"id":"crossover","kind":"term","name":"Crossover in trials","route":"/terms/crossover/"},{"id":"estimand","kind":"term","name":"Estimands and intercurrent events (ICH E9(R1))","route":"/terms/estimand/"},{"id":"mcrpc-mhspc","kind":"term","name":"mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)","route":"/terms/mcrpc-mhspc/"},{"id":"myelosuppression-after-rlt","kind":"term","name":"Myelosuppression after radioligand therapy","route":"/terms/myelosuppression-after-rlt/"},{"id":"salivary-gland-toxicity","kind":"term","name":"Salivary gland toxicity (xerostomia) from PSMA radioligand therapy","route":"/terms/salivary-gland-toxicity/"}],"roadmap":[{"id":"psma-theranostics-roadmap","kind":"roadmap","name":"PSMA theranostics roadmap: antigen discovery → PSMA PET → 177Lu-PSMA-617 → earlier lines and alpha","route":"/roadmaps/psma-theranostics-roadmap/"},{"id":"radiopharma-roadmap","kind":"roadmap","name":"Radiopharmaceutical roadmap: iodine → lutetium → actinium","route":"/roadmaps/radiopharma-roadmap/"}],"paper":[{"id":"paper-psmafore-lancet-2024","kind":"paper","name":"PSMAfore: 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor in taxane-naive mCRPC","route":"/key-papers/paper-psmafore-lancet-2024/"},{"id":"paper-vision-nejm-2021","kind":"paper","name":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer","route":"/key-papers/paper-vision-nejm-2021/"}],"section":[{"id":"f-radioligand-therapy","kind":"section","name":"Radioligand therapy","route":"/fronts/f-radioligand-therapy/"}],"pairing":[{"id":"docetaxel-then-lu177-psma","kind":"pairing","name":"Docetaxel (taxane chemotherapy) then 177Lu-PSMA-617","route":"/pairings/docetaxel-then-lu177-psma/"}],"trial":[{"id":"enza-p","kind":"trial","name":"ENZA-p","route":"/trials/enza-p/"}]}}