Drug Utilisation of Radium-223 Under Routine Clinical Practice (DIRECT) in Europe: A Post-Authorisation Safety Study

Radium-223 is indicated for adults with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases, without visceral metastases, who progress after at least (≥) two lines of or are ineligible for other systemic therapies (besides luteinising hormone-releasing hormone analogues). Radium-223 is contraindicated in combination with abiraterone acetate and prednisone/prednisolone. Point 2 and the contraindication above were added to the 2018 European Medicines Agency (EMA) label. In the observational cohort study reported here, we evaluated compliance with the 2018 revised label.

The proportion of patients with mCRPC who initiated radium-223 in the Netherlands, Germany and Denmark was analysed descriptively before (2013-2017) and after (2019-2020) the label change, allowing ≥ 6 months of follow-up. No a priori hypotheses were evaluated.

A total of 1070 patients were included in this observational cohort study (before/after the label change: Netherlands [243/53]; Germany [580/71]; Denmark [60/63]). Radium-223 use with abiraterone acetate or other systemic mCRPC therapies was limited and decreased after the label change in the Netherlands and Germany; in Denmark, combined use was not observed before the label change and was observed only rarely after the label change. After the label change, radium-223 use without ≥ 2 prior lines of systemic mCRPC therapy decreased in all countries, despite remaining relatively common in the Netherlands and Germany.

Radium-223 use in combination with abiraterone acetate or other systemic mCRPC therapies largely aligned with the 2018 EMA label change. However, after the label change, radium-223 use without ≥ 2 prior lines of systemic mCRPC therapy remained relatively common in the Netherlands and Germany, possibly because radium-223 was previously recommended as first-line treatment for frail patients, and doctors still may consider it for use in these cases. We could not assess patients' eligibility for other systemic mCRPC therapies; therefore, these findings may partly reflect radium-223 on-label use in patients with contraindications for other systemic therapies.

EUPAS37163.