{"entity":{"id":"peace-3","kind":"trial","name":"PEACE-3 (EORTC 1333)","aka":["PEACE-3","PEACE III","EORTC 1333-GUCG"],"tldr":"Combining the bone-seeking radioactive drug radium-223 with enzalutamide made men live about six months longer, and the fractures that sank the earlier version of this idea were prevented by giving bone-protecting drugs to everyone.","summary":"ERA 223 combined radium-223 with abiraterone and produced more fractures and more deaths, and the trial was unblinded early. PEACE-3 is the trial that tested the same idea properly, with enzalutamide instead of abiraterone and, from March 2018, with bone-protecting agents made mandatory for every participant.\n\nFrom November 2015 to March 2023, 446 men were randomly assigned to enzalutamide alone (224) or enzalutamide with six cycles of radium-223 (222). The final overall survival analysis was triggered on 1 May 2025.\n\nWith a median follow-up of 58 months and 317 deaths, the hazard ratio for overall survival was 0.76 (95 percent confidence interval 0.60 to 0.96, p=0.0096), crossing the predefined significance level of 0.0248. Median overall survival was 32.6 months (29.3 to 38.2) with enzalutamide alone and 38.2 months (33.1 to 44.8) with the combination. The hazard ratio for radiological progression-free survival, the primary endpoint, was 0.71 (0.57 to 0.89).\n\nThe combination costs toxicity. Grade 3 or worse treatment-emergent adverse events rose from 57.6 to 69.3 percent and treatment-related grade 3 or worse events from 18.8 to 28.9 percent, most frequently hypertension. The trial's own conclusion is that co-administration of a bone-protecting agent is required.\n\nPEACE-3 is the rare case of a field going back to a combination that harmed people, working out why, fixing it and proving it works.","status":"positive","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT02194842","url":"https://clinicaltrials.gov/study/NCT02194842"},{"label":"PEACE-3 final overall survival (Annals of Oncology 2026)","url":"https://doi.org/10.1016/j.annonc.2026.02.009"},{"label":"NICE TA412: radium-223 dichloride for treating hormone-relapsed prostate cancer with bone metastases","url":"https://www.nice.org.uk/guidance/ta412"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["targeted-alpha-therapy","androgen-deprivation"],"targets":["androgen-receptor"],"drugs":["radium-223","enzalutamide","denosumab","zoledronic-acid"],"companies":["curie-nki-eortc","bayer"],"institutions":[],"pathways":[],"terms":["bone-metastases","castration-resistance","arpi"],"trials":["era-223","alsympca","vision"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02194842","phase":"3","setting":"Asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer with bone metastases: enzalutamide 160 mg daily alone against enzalutamide with six monthly injections of radium-223 at 55 kBq/kg, with bone-protecting agents made mandatory for all patients from March 2018, with radiological progression-free survival as the primary endpoint","sponsor":"European Organisation for Research and Treatment of Cancer, Genito-Urinary Cancers Group","result":"Median overall survival 38.2 months with enzalutamide plus radium-223 against 32.6 months with enzalutamide alone (hazard ratio 0.76, 95 percent confidence interval 0.60 to 0.96, p=0.0096); radiological progression-free survival hazard ratio 0.71 (0.57 to 0.89). Bone-protecting agents mandatory.","yearReported":2026,"enrolled":446,"enrolledBasis":"randomised","enrolledNote":"446 men were randomly assigned between November 2015 and March 2023.","outcomes":[{"endpoint":"Overall survival (median)","unit":"months","arms":[{"name":"Enzalutamide with radium-223","n":222,"value":38.2},{"name":"Enzalutamide alone","n":224,"value":32.6}],"hr":0.76,"ci":[0.6,0.96],"p":"0.0096","source":"https://doi.org/10.1016/j.annonc.2026.02.009"},{"endpoint":"Radiological progression-free survival","primary":true,"arms":[{"name":"Enzalutamide with radium-223","n":222},{"name":"Enzalutamide alone","n":224}],"hr":0.71,"ci":[0.57,0.89],"source":"https://doi.org/10.1016/j.annonc.2026.02.009"},{"endpoint":"Grade 3 or worse treatment-emergent adverse events","unit":"%","arms":[{"name":"Enzalutamide with radium-223","n":222,"value":69.3},{"name":"Enzalutamide alone","n":224,"value":57.6}],"source":"https://doi.org/10.1016/j.annonc.2026.02.009"}],"replication":"ERA 223 tested the same concept with abiraterone and without mandatory bone protection, and found no benefit and a fracture rate of 29 against 11 percent; the difference between the two trials is the bone-protecting agent and the partner drug."},"route":"/trials/peace-3/","neighbours":{"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"androgen-deprivation","kind":"technology","name":"Androgen deprivation & AR pathway inhibitors","route":"/technologies/androgen-deprivation/"},{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","route":"/technologies/targeted-alpha-therapy/"}],"target":[{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"}],"drug":[{"id":"denosumab","kind":"drug","name":"Denosumab","route":"/drugs/denosumab/"},{"id":"enzalutamide","kind":"drug","name":"Enzalutamide","route":"/drugs/enzalutamide/"},{"id":"radium-223","kind":"drug","name":"Radium-223 dichloride","route":"/drugs/radium-223/"},{"id":"zoledronic-acid","kind":"drug","name":"Zoledronic acid","route":"/drugs/zoledronic-acid/"}],"company":[{"id":"bayer","kind":"company","name":"Bayer","route":"/companies/bayer/"},{"id":"curie-nki-eortc","kind":"company","name":"EORTC","route":"/companies/curie-nki-eortc/"}],"term":[{"id":"arpi","kind":"term","name":"Androgen receptor pathway inhibitor (ARPI)","route":"/terms/arpi/"},{"id":"bone-metastases","kind":"term","name":"Bone metastases and skeletal-related events","route":"/terms/bone-metastases/"},{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"},{"id":"prostate-crpc-sequencing","kind":"term","name":"What follows what in castration-resistant prostate cancer","route":"/terms/prostate-crpc-sequencing/"}],"trial":[{"id":"alsympca","kind":"trial","name":"ALSYMPCA","route":"/trials/alsympca/"},{"id":"era-223","kind":"trial","name":"ERA 223","route":"/trials/era-223/"},{"id":"vision","kind":"trial","name":"VISION","route":"/trials/vision/"}]}}