European Medicines Agency (EMA) has recommended contraindicating the use of the prostate cancer medicine Xofigo (radium-223 dichloride) with Zytiga ( abiraterone acetate) and prednisone/prednisolone, due to an increased risk of death and fractures with this combination.
EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has reviewed the preliminary data from an ongoing clinical study in metastatic prostate cancer patients. In this study 34.7% of patients treated with Xofigo, Zytiga and prednisone/prednisolone have died so far, compared with 28.2% of patients given placebo, Zytiga and prednisone/prednisolone.
Fractures have also occurred more frequently with the Xofigo combination than the placebo combination (26% versus 8.1%).
In view of the seriousness of the events reported, the PRAC has taken action by introducing a contraindication as a temporary measure to protect patients’ safety while an in-depth review of the benefits and risks of Xofigo is ongoing.
Xofigo is currently authorised for use in men whose prostate cancer has spread to the bones and is causing symptoms. The ongoing clinical study includes metastatic prostate cancer patients who have not previously received chemotherapy and who have no symptoms or only mild symptoms, such as pain. Patients have completed the Xofigo part of the study, and the combination is no longer being used; all the patients involved are being monitored closely.
Healthcare professionals in the EU must not use a combination of Xofigo with the anti-androgen Zytiga and prednisone/prednisolone, and should stop this combination in men currently treated with it and review the treatment for these patients.
Both medicines can continue to be used separately, in line with the recommendations in their product information.
Healthcare professionals are also warned that the safety and efficacy of Xofigo in combination with a class of second generation androgen receptor antagonists, such as Xtandi ( enzalutamide), have not been established.
These are temporary measures until the ongoing in-depth review of the benefits and risks of Xofigo is complete. EMA will communicate further at the conclusion of the review.
The ongoing study of Xofigo in combination with Zytiga and prednisone/prednisolone included patients with castration-resistant prostate cancer that has spread mainly to the bones, who have no symptoms or only mild symptoms and who have not been treated with chemotherapy.
Xofigo was authorised in the European Union in November 2013.
The review of Xofigo has been initiated at the request of the European Commission, under Article 20 of Regulation (EC) No 726/2004.
The review is being carried out by the, the EMA’s Committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations.
During the review, the PRAC made provisional recommendations to protect public health. This will be forwarded to the European Commission (EC), which will issue a provisional legally binding decision applicable in all EU Members States.
Once the PRAC review is concluded, any further recommendations will be forwarded to the Committee for Medicinal Products for Human Use (CHMP), responsible for evaluating medicines for human use, which will adopt a final opinion.
The final stage of the review procedure is the adoption by the EC of a legally binding decision applicable in all EU Member States.