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

Background: Radium-223 is indicated for adults with (1) metastatic castration-resistant prostate cancer (mCRPC) with symptomatic bone metastases and no visceral metastases who (2) experience progression after ≥ 2 prior lines of systemic mCRPC therapy (except luteinising hormone–releasing hormone analogues) or those ineligible for other systemic mCRPC therapies, and (3) is contraindicated for concomitant use with abiraterone acetate and prednisone/prednisolone. Items 2 and 3 were added to the European Medicines Agency (EMA) label in 2018.

Objectives: This study’s aim was to determine the proportion of patients who receive radium-223 in compliance with the new 2018 EMA label by comparing use before and after the label change.

Methods: This was an observational cohort drug utilisation study in Europe (EUPAS37163), including patients with mCRPC of any age who were new users of radium-223. Secondary data sources included the Castration-Resistant Prostate Cancer Registry in the Netherlands (NL), the German Pharmacoepidemiological Research Database in Germany (DE), and the Danish National Patient Registry with review of individual medical records at 2 large hospitals in Denmark (DK). Data collected before (November 2013–November 2017) and after (April 2019–October 2020 [NL only] or December 2020) the label change, including ≥ 6 months of potential follow-up, were analyzed using descriptive statistics.

Results: This study included 1,070 patients (before, after: NL [243, 53]; DE [580, 71]; DK [60, 63]). Radium-223 use with abiraterone (patients before, after: NL [6.6%, 1.9%]; DE [22.9%, 4.2%]; DK [0.0%, 1 ≤ n < 5—number masked due to privacy regulations]) and with other systemic mCRPC therapies (patients before, after: NL [14.4%, 9.4%]; DE [27.3%, 11.8%]; DK [0.0%, 1 ≤ n < 5]) was uncommon and generally decreased after the label change. Similarly, radium-223 use without ≥ 2 prior lines of systemic mCRPC therapy decreased after the label change, despite remaining relatively common in NL and DE (patients before, after: NL [46.5%, 39.6%]; DE [55.9%, 26.5%]; DK [26.7%, 1 ≤ n < 5]).

Conclusions: Use of radium-223 in combination with abiraterone or other systemic mCRPC therapies was largely in line with the 2018 EMA label. However, use of radium-223 without ≥ 2 prior lines of systemic mCRPC therapy remained relatively common after the label change in NL and DE; this may be because clinical guidelines before the label change recommended radium-223 as a first-line option in mCRPC, especially in frail patients, possibly leading doctors to still consider its use in the first line in these cases. Of note, patients’ eligibility for other systemic mCRPC therapies could not be determined, so our findings reflect, in part, use in patients for whom other systemic therapies were contraindicated.