# ERA 223

Source: https://onco.cc/trials/era-223/  
OnCo record `era-223` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

The 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.

At 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).

The 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.

PEACE-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.

## Fields

- Kind: Trial
- Status: negative
- Last checked: 2026-09-25
- Also known as: ERA 223; ERA223
- Registry id: 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
- Enrolled: 806
- 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.
- Outcomes: Symptomatic skeletal event-free survival (median): Radium-223 with abiraterone and prednisone 22.3 months vs Placebo with abiraterone and prednisone 26 months, HR 1.122; Fracture, any grade: Radium-223 with abiraterone and prednisone 29% vs Placebo with abiraterone and prednisone 11%
- 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.

## Sources

- ClinicalTrials.gov NCT02043678: https://clinicaltrials.gov/study/NCT02043678
- ERA 223 (Lancet Oncology 2019): https://doi.org/10.1016/S1470-2045(18)30860-X

## Connected records

- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Androgen deprivation & AR pathway inhibitors](https://onco.cc/technologies/androgen-deprivation/), [Targeted alpha therapy](https://onco.cc/technologies/targeted-alpha-therapy/)
- drugs: [Abiraterone acetate](https://onco.cc/drugs/abiraterone/), [Prednisone](https://onco.cc/drugs/prednisone/), [Radium-223 dichloride](https://onco.cc/drugs/radium-223/)
- companies: [Bayer](https://onco.cc/companies/bayer/)
- terms: [Bone metastases and skeletal-related events](https://onco.cc/terms/bone-metastases/), [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [Prostate cancer programmes that failed, and what each failure taught](https://onco.cc/terms/prostate-failed-programmes/)
- trials: [ALSYMPCA](https://onco.cc/trials/alsympca/), [PEACE-3 (EORTC 1333)](https://onco.cc/trials/peace-3/)

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