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Radium-223 extended OS, reduced risk for death in castration-resistant prostate cancer
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Radium Ra 223 dichloride significantly prolonged OS in patients with castration-resistant prostate cancer and bone metastases, reducing the risk for death by 30% compared with placebo, according to results of a phase 3 study.
“Unlike deaths from many other types of cancer, deaths from prostate cancer are often due to bone disease and its complications,” Chris Parker, MD, FRCR, a consultant clinical oncologist at Royal Marsden Hospital in Sutton, Surrey, the United Kingdom, and colleagues wrote. “Current bone-targeted therapies have not been shown to improve survival, and the benefits derived from bisphosphonates, denosumab and existing radioisotope treatments are primarily limited to pain relief and delay of skeletal events.”
Prior phase 1/2 studies have reported that radium Ra 223 dichloride (radium-223; Xofigo, Bayer) exhibited a favorable safety profile, with minimal myelotoxicity, in patients with bone metastases. Additionally, phase 2 studies have indicated that radium-223 reduced pain, improved disease-related biomarkers, and may have a survival benefit among patients with castration-resistant prostate cancer and bone metastases.
To determine the effect of radium-223 vs. placebo on survival, Parker and colleagues conducted a phase 3, randomized, double blind study in patients with castration-resistant prostate cancer and bone metastases.
The ALSYMPCA study included 921 patients who had received, were not eligible to receive or had declined docetaxel.
Researchers randomly assigned patients in a 2:1 ratio to six IV injections of radium-223, at a dose of 50 kBq/kg of body weight, or a matching placebo once every 4 weeks.
A prespecified interim analysis — performed after 314 deaths had occurred — evaluated the effect of radium-223 vs. placebo on survival. An updated analysis — performed after 528 deaths — was conducted before crossover from placebo to radium-223.
OS served as the primary endpoint. Major secondary efficacy endpoints included time to the first symptomatic skeletal event, time to an increase in PSA levels and various biochemical endpoints.
The interim analysis consisted of 809 patients. Results showed radium-223 was associated with significantly improved median OS (14 months vs. 11.2 months; HR=0.70; 95% CI, 0.55-0.88).
The updated analysis, which included 921 patients, further established the median OS benefit associated with radium-223 survival (14.9 months vs. 11.3 months; HR=0.70; 95% CI, 0.58-0.83).
Researchers reported that 191 of 541 (35%) patients assigned to radium-223 died, compared with 123 of 263 (46%) patients assigned to placebo.
Researchers observed the survival benefit of radium-223 across all subgroups. The treatment also was associated with low myelosuppression rates and fewer adverse events than placebo.
Disclosure: The study was supported by Algeta and Bayer HealthCare Pharmaceuticals. See the full study for a list of the researchers’ relevant financial disclosures.
Perspective
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Robert Dreicer, MD, FACP, FASCO
The significance of radium-223 is that it is a first-in-class type of therapy, being an alpha emitter. It is clinically significant because this is an agent that has brought the demonstrative ability to improve survival and decrease symptomatic skeletal events. The therapy-related toxicity is relatively modest. That would make it amenable for combination therapies.
The take-home message is that radium-223 is a novel therapy; however, clinicians need to be aware of the fact that — although this is an agent that is active in patients with bone metastases — it does not exhibit activity in soft tissue disease. For patients with bone-related disease, radium-223 clearly has the potential to be a useful adjunct to other available therapies. I do not expect this to drastically change the treatment paradigm; it does represent another new agent incorporated into the paradigm, although we will have to work out how to do that.
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