{"entity":{"id":"era-223","kind":"trial","name":"ERA 223","aka":["ERA 223","ERA223"],"tldr":"Combining a bone-seeking radioactive drug with abiraterone did not help, and it nearly tripled the rate of broken bones. The trial was unblinded early and the combination is now contraindicated.","summary":"ERA 223 is the clearest example in prostate cancer of a combination that was harmful, and of a harm that was preventable. It randomised 806 men with chemotherapy-naive, bone-metastatic castration-resistant prostate cancer to abiraterone with prednisone or prednisolone plus either radium-223 or placebo.\n\nThe study was unblinded prematurely on 17 November 2017 after an unplanned ad hoc analysis found more fractures and more deaths in the radium-223 group, although by then every man had finished radium-223 or placebo.\n\nAt the primary analysis (data cutoff 15 February 2018, median follow-up 21.2 months) the primary endpoint had not been met: 196 of 401 men (49 percent) on radium-223 and 190 of 405 (47 percent) on placebo had a symptomatic skeletal event or died, median symptomatic skeletal event-free survival 22.3 months (95 percent confidence interval 20.4 to 24.8) against 26.0 months (21.8 to 28.3), hazard ratio 1.122 (0.917 to 1.374, p=0.2636).\n\nThe fracture figures are the reason the trial is remembered. Fractures of any grade occurred in 112 of 392 men (29 percent) on radium-223 and 45 of 394 (11 percent) on placebo; grade 3 to 4 fractures in 36 (9 percent) against 12 (3 percent). Bone-protecting agents were not mandatory.\n\nPEACE-3 later tested the same concept with enzalutamide and with bone-protecting agents mandatory for everyone, and found an overall survival benefit with a hazard ratio of 0.76. The difference between the two trials is the single most useful practical fact about radium-223 combinations: give the bone-protecting agent.","status":"negative","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT02043678","url":"https://clinicaltrials.gov/study/NCT02043678"},{"label":"ERA 223 (Lancet Oncology 2019)","url":"https://doi.org/10.1016/S1470-2045(18)30860-X"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["targeted-alpha-therapy","androgen-deprivation"],"targets":[],"drugs":["radium-223","abiraterone","prednisone"],"companies":["bayer"],"institutions":[],"pathways":[],"terms":["bone-metastases","castration-resistance"],"trials":["peace-3","alsympca"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02043678","phase":"3","setting":"Chemotherapy-naive, asymptomatic or mildly symptomatic castration-resistant prostate cancer with bone metastases: abiraterone acetate 1000 mg daily with prednisone or prednisolone 5 mg twice daily for everyone, plus up to six intravenous injections of radium-223 at 55 kBq/kg or placebo every 4 weeks, with symptomatic skeletal event-free survival as the primary endpoint","sponsor":"Bayer","result":"Median symptomatic skeletal event-free survival 22.3 against 26.0 months (hazard ratio 1.122, 95 percent confidence interval 0.917 to 1.374, p=0.2636): no benefit. Fractures of any grade in 29 against 11 percent, grade 3 to 4 fractures in 9 against 3 percent.","yearReported":2019,"enrolled":806,"enrolledBasis":"randomised","enrolledNote":"806 men were randomly assigned at 165 oncology and urology centres in 19 countries; the study was unblinded prematurely on 17 November 2017.","outcomes":[{"endpoint":"Symptomatic skeletal event-free survival (median)","primary":true,"unit":"months","arms":[{"name":"Radium-223 with abiraterone and prednisone","n":401,"value":22.3},{"name":"Placebo with abiraterone and prednisone","n":405,"value":26}],"hr":1.122,"ci":[0.917,1.374],"p":"0.2636","source":"https://doi.org/10.1016/S1470-2045(18)30860-X"},{"endpoint":"Fracture, any grade","unit":"%","arms":[{"name":"Radium-223 with abiraterone and prednisone","n":392,"value":29},{"name":"Placebo with abiraterone and prednisone","n":394,"value":11}],"source":"https://doi.org/10.1016/S1470-2045(18)30860-X"}],"replication":"PEACE-3 tested the same combination concept with enzalutamide and mandatory bone-protecting agents and found an overall survival hazard ratio of 0.76 (0.60 to 0.96), so the harm is attributable to the missing bone protection rather than to the radioligand alone."},"route":"/trials/era-223/","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/"}],"drug":[{"id":"abiraterone","kind":"drug","name":"Abiraterone acetate","route":"/drugs/abiraterone/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"},{"id":"radium-223","kind":"drug","name":"Radium-223 dichloride","route":"/drugs/radium-223/"}],"company":[{"id":"bayer","kind":"company","name":"Bayer","route":"/companies/bayer/"}],"term":[{"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-failed-programmes","kind":"term","name":"Prostate cancer programmes that failed, and what each failure taught","route":"/terms/prostate-failed-programmes/"}],"trial":[{"id":"alsympca","kind":"trial","name":"ALSYMPCA","route":"/trials/alsympca/"},{"id":"peace-3","kind":"trial","name":"PEACE-3 (EORTC 1333)","route":"/trials/peace-3/"}]}}