The changing role of radium-223 in mCRPC: has the European Medicines Agency missed the mark with revising the label?

Radium-223 is a life prolonging treatment in symptomatic men with metastatic castrate resistant prostate cancer (mCRPC) and bone metastases, but no visceral disease, regardless of prior treatment with docetaxel. Together with four other drugs (i.e. abiraterone, cabazitaxel, docetaxel, enzalutamide), it has been available for clinical use since 2013 and has been shown to also provide benefits in quality-of-life and societal benefits. However, in 2018 the European Medicines Agency (EMA) ruled to restrict the use of radium-223 to a more advanced disease setting after at least 2 lines of one or the other life prolonging agent. This decision was triggered by the results of a safety interim analysis of ERA-223, a trial investigating the combination of radium-223 and abiraterone versus abiraterone alone in patients without prior chemotherapy (with the exception of adjuvant treatment) with asymptomatic bone predominant mCRPC. That safety analysis showed an early increased risk of fracture and deaths with the combination treatment. This review critically appraises the available and emerging data with radium-223 treatment in an attempt to assess the appropriateness of the revised label of radium-223