{"entity":{"id":"enza-p","kind":"trial","name":"ENZA-p","aka":["ANZUP 1901"],"tldr":"Adding the radioactive drug lutetium-PSMA to the hormone drug enzalutamide, with the dose adjusted according to a mid-treatment PET scan, kept prostate cancer under control for longer and helped men with high-risk metastatic disease live longer than enzalutamide on its own.","summary":"ENZA-p (ANZUP 1901) was an open-label, randomised, controlled phase 2 trial at 15 Australian hospitals in men with metastatic castration-resistant prostate cancer who had not yet received docetaxel or an androgen receptor pathway inhibitor for mCRPC, had PSMA-PET-positive disease, and carried at least two risk factors for early progression on enzalutamide. Patients received oral enzalutamide alone or with adaptive-dosed intravenous 177Lu-PSMA-617 (two or four cycles of 7.5 GBq every 6-8 weeks, guided by an interim PSMA PET-CT at week 12). The primary endpoint was PSA progression-free survival.\n\nAmong 162 randomised patients, adding LuPSMA improved PSA progression-free survival (13.0 vs 7.8 months, HR 0.43, p<0.0001) and PSA response rate (93% vs 68%) at the interim analysis. At longer follow-up (median 34 months), overall survival also favoured the combination (median 34 vs 26 months, HR 0.55, p=0.0053), along with better quality-of-life deterioration-free survival for physical function and overall health. Grade 3-5 adverse events were comparable between arms, with anaemia and thrombocytopenia occurring only in the combination group; there were no treatment-related deaths.\n\nENZA-p is the first randomised trial to show an overall survival benefit for adding LuPSMA to an ARPI ahead of chemotherapy, using biomarker-guided adaptive dosing via interim PSMA PET, and it has prompted phase 3 evaluation of the same combination strategy.","status":"active","asOf":"2026-09-22","links":[{"label":"Lancet Oncology 2024: ENZA-p interim results","url":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00135-9/abstract"},{"label":"Lancet Oncology 2025: ENZA-p overall survival and quality of life (secondary outcomes)","url":"https://pubmed.ncbi.nlm.nih.gov/39956124/"},{"label":"ClinicalTrials.gov: NCT04419402","url":"https://clinicaltrials.gov/study/NCT04419402"}],"tags":["radioligand therapy","prostate cancer","combination therapy","adaptive dosing"],"related":["pluvicto","enzalutamide","prostate-mcrpc","psma-pet","psmafore","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04419402","phase":"2","setting":"Metastatic castration-resistant prostate cancer, PSMA-PET-positive, no prior docetaxel or ARPI for mCRPC, with at least two risk factors for early progression on enzalutamide; first-line mCRPC","sponsor":"Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)","result":"Adding adaptive-dosed 177Lu-PSMA-617 to enzalutamide improved PSA progression-free survival (13.0 vs 7.8 months, HR 0.43, p<0.0001) and, at longer follow-up, overall survival (median 34 vs 26 months, HR 0.55, 95% CI 0.36-0.84, p=0.0053) (Lancet Oncology 2024 and 2025)","yearReported":2025,"enrolled":162,"enrolledBasis":"registry","outcomes":[{"endpoint":"PSA progression-free survival","primary":true,"unit":"months","arms":[{"name":"Enzalutamide + adaptive-dosed 177Lu-PSMA-617","n":83,"value":13},{"name":"Enzalutamide alone","n":79,"value":7.8}],"hr":0.43,"ci":[0.29,0.63],"p":"<0.0001","source":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00135-9/abstract"},{"endpoint":"Overall survival (longer follow-up)","unit":"months","arms":[{"name":"Enzalutamide + adaptive-dosed 177Lu-PSMA-617","n":83,"value":34},{"name":"Enzalutamide alone","n":79,"value":26}],"hr":0.55,"ci":[0.36,0.84],"p":"0.0053","source":"https://pubmed.ncbi.nlm.nih.gov/39956124/"},{"endpoint":"PSA response rate (≥50% decline)","unit":"%","arms":[{"name":"Enzalutamide + 177Lu-PSMA-617","n":83,"value":93},{"name":"Enzalutamide alone","n":79,"value":68}]},{"endpoint":"Grade 3-5 adverse events (secondary-outcomes report)","unit":"%","arms":[{"name":"Enzalutamide + 177Lu-PSMA-617","n":81,"value":46},{"name":"Enzalutamide alone","n":79,"value":44}],"source":"https://pubmed.ncbi.nlm.nih.gov/39956124/"}]},"route":"/trials/enza-p/","neighbours":{"drug":[{"id":"enzalutamide","kind":"drug","name":"Enzalutamide","route":"/drugs/enzalutamide/"},{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"}],"indication":[{"id":"prostate-mcrpc","kind":"indication","name":"Metastatic castration-resistant prostate cancer","route":"/indications/prostate-mcrpc/"}],"technology":[{"id":"psma-pet","kind":"technology","name":"PSMA PET","route":"/technologies/psma-pet/"}],"trial":[{"id":"psmafore","kind":"trial","name":"PSMAfore","route":"/trials/psmafore/"}],"isotope":[{"id":"lu-177","kind":"isotope","name":"Lutetium-177","route":"/isotopes/lu-177/"}]}}