Radium-223 dichloride (Xofigo) significantly improved overall survival and caused few adverse events in men with castration-resistant prostate cancer (CRPC) that had metastasized to bone, researchers reported (N Engl J Med. 2013;369:213-223).
Approved by the FDA in May 2013 for the treatment of men with symptomatic CRPC that has metastasized only to bones (no other organs), radium-223 is an alpha emitter. The agent binds with minerals in bone to deliver radiation directly to bone tumors, which limits damage to healthy tissue.
The phase 3 trial pointing to the extended survival benefits of radium-223 involved men with CRPC and bone metastases who had, variously: received, were not eligible to receive, or had declined to receive, docetaxel. The Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) investigators, working in 136 centers across 19 countries, randomly assigned 614 patients to receive six injections of radium-223 and 307 patients to receive matching placebo. Injections were administered every 4 weeks.
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A prespecified interim analysis of the effect of radium-223 on survival was conducted when 314 deaths had occurred. Because that analysis showed a strong survival advantage and an acceptable safety profile for radium-223, the trial was discontinued and patients receiving placebo were switched to radium-223. The data from the interim analysis were updated after 528 deaths had occurred.
In the interim analysis, which included 809 participants, median overall survival was 30% lower for patients given radium-223 compared with patients given placebo (14.0 months vs 11.2 months). This survival benefit was confirmed in the updated analysis: Among the 921 study participants included in the update, median overall survival was 14.9 months for those receiving radium-223, compared with 11.3 months for the placebo users.
Radium-223 also showed a benefit compared with placebo in all main secondary efficacy end points, including time to first symptomatic skeletal event and various biochemical end points. In addition, radium-223 was associated with low myelosuppression rates and fewer adverse events.
The proportion of patients experiencing adverse events was consistently lower in the radium-223 group than in the placebo group (93% vs 96%), including for grade 3 or 4 adverse events (56% vs 62%), serious adverse events (47% vs 60%), and need to discontinue treatment due to adverse events (16% vs 21%).
The authors concluded that the excellent safety profile of radium-223 and its nonoverlapping mechanism of action with various other prostate cancer drugs make radium-223 potentially suitable for use either sequentially or in combination with those agents.
