Use of the novel radiopharmaceutical radium-223 dichloride (Xofigo, Bayer) in prostate cancer should be restricted, according to the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC).

PRAC first noted concerns about this product in December 2017. At the time, the committee noted that it was investigating reports of an increase in deaths and fractures in an ongoing trial exploring the radiopharmaceutical for an unapproved use.

Now, PRAC has said that it decided, following a review of those data, to recommend restricting the use of radium-223 dichloride to patients who have had two previous treatments for metastatic prostate cancer or who cannot receive other treatments.

PRAC also confirmed its previous interim recommendation that the radium-233 dichloride must not be used with abiraterone acetate (Zytiga, Janssen) and prednisone/prednisolone.

Reports From Clinical Trials

PRAC gave details of the problem back in December 2017. The reports of an increase in deaths and fractures came from an ongoing trial (ERA223) that was comparing the radiopharmaceutical with placebo in men with prostate cancer who were already taking abiraterone acetate and a steroid (prednisone or prednisolone).

This trial included patients with prostate cancer who have no symptoms or mild symptoms, such as pain, the committee noted. The investigators were exploring an unapproved use of the radiopharmaceutical, the committee emphasized.

Radium-223 dichloride is currently approved for use in the treatment of castration-resistant prostate cancer in patients who have symptomatic bone metastases.

The product has been on the market for about 5 years. It was approved in the United States in May 2013 by the Food and Drug Administration and approved in Europe in November 2013.

Favorable Benefit/Risk Ratio When Used as Approved

Also in December 2017, the manufacturer of the radiopharmaceutical, Bayer, announced in a press statement that the trial had been unblinded on the recommendation of an independent data monitoring committee (IDMC).

"The IDMC recommendation is due to the observation of an imbalance of more fractures and deaths in the treatment arm investigating radium-223 in combination with abiraterone acetate and prednisone/prednisolone," the company said.

"Patient safety is our top priority. We are therefore unblinding the study to analyze the data thoroughly," explained Mike Devoy, a chief medical officer at Bayer.

"It is important to note that, based on available data from previous trials as well as real-world use, the benefit-risk profile of Xofigo in its approved indication remains favorable," he added.