Radium-223 dichloride (Xofigo▼): do not use in combination with abiraterone and prednisone/prednisolone, following clinical trial signal of increased risk of death and fractures
A European review has begun into the safety of radium-223 dichloride following an observed increase in the incidence of deaths and fractures in patients with chemotherapy-naive metastatic castration-resistant prostate cancer receiving radium-223 dichloride in combination with abiraterone acetate (Zytiga) and prednisone/prednisolone as part of a clinical trial. Until full analysis of the results is completed, do not treat patients with radium-223 dichloride in combination with abiraterone acetate and prednisone/prednisolone.
On 8 March 2018, the European Medicines Agency (EMA) recommended contraindicating the use of ▼Xofigo (radium-223 dichloride) with Zytiga (abiraterone acetate) and prednisone/prednisolone until the completion of the ongoing in-depth review of the benefits and risks of Xofigo. The EMA also advised that the safety and efficacy of Xofigo in combination with a class of medicines called second-generation androgen receptor antagonists, such as Xtandi (enzalutamide), have not been established. . A has been sent to relevant healthcare professionals in the UK to advise of these recommendations.
Xofigo▼ is licensed for the treatment of men with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease.
Preliminary data from a randomised, double-blind, placebo-controlled study showed an increased incidence of deaths (27% versus 20%) and fractures (24% versus 7%) among patients receiving Xofigo in combination with abiraterone acetate and prednisone/prednisolone (n=401) compared to patients receiving placebo in combination with abiraterone acetate and prednisone/prednisolone (n=405). This study in asymptomatic or mildly symptomatic chemotherapy-naive patients with bone-predominant metastatic castration-resistant prostate cancer was unblinded early based on an Independent Data Monitoring Committee recommendation.
Until full analysis of the results is completed, do not use radium-223 dichloride in combination with abiraterone acetate and prednisone/prednisolone to treat metastatic castration-resistant prostate cancer (see ). Further advice will be communicated as appropriate at the end of the review.
Article citation: Drug Safety Update volume 11 issue 5; December 2017: 3.