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

Area of Science:

• Oncology
• Radiopharmaceutical Therapy
• Prostate Cancer Research

Background:

• Radium-223 is approved for metastatic castration-resistant prostate cancer (mCRPC) with bone metastases, excluding visceral disease, after ≥2 prior systemic therapies or ineligibility.
• A 2018 European Medicines Agency (EMA) label update revised criteria and added a contraindication for combining radium-223 with abiraterone acetate and prednisone/prednisolone.
• Compliance with the revised 2018 EMA label for radium-223 use in mCRPC was evaluated in a multi-country observational cohort study.

Purpose of the Study:

• To assess adherence to the 2018 EMA revised label for radium-223 in patients with mCRPC.
• To analyze the utilization patterns of radium-223 before and after the 2018 label update across different European countries.
• To investigate the frequency of radium-223 use in combination with other systemic therapies and in relation to prior treatment lines.

Main Methods:

• An observational cohort study analyzed radium-223 initiation in the Netherlands, Germany, and Denmark.
• Data were collected for periods before (2013-2017) and after (2019-2020) the 2018 EMA label change.
• Descriptive analysis focused on the proportion of patients receiving radium-223, including its use with other systemic therapies and prior treatment lines, with at least 6 months of follow-up.

Main Results:

• A total of 1070 patients were included in the study.
• Radium-223 use in combination with abiraterone acetate or other systemic therapies decreased post-label change in the Netherlands and Germany, and was rare in Denmark.
• Use of radium-223 without at least two prior systemic mCRPC therapies decreased but remained relatively common in the Netherlands and Germany after the label update.

Conclusions:

• Radium-223 use largely aligned with the 2018 EMA label regarding combinations with other systemic therapies.
• Continued use of radium-223 without meeting prior treatment line criteria in the Netherlands and Germany may reflect historical recommendations for frail patients or physician discretion.
• The study could not assess contraindications for other systemic therapies, potentially influencing the interpretation of on-label radium-223 use.