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In men with castration-resistant prostate cancer and symptomatic bone metastases, the investigational radiopharmaceutical radium-223 (Alpharadin) improved overall survival by 30% and time to first skeletal-related event by 39% compared with placebo.
Stockholm, Sweden-In men with castration-resistant prostate cancer and symptomatic bone metastases, the investigational radiopharmaceutical radium-223 (Alpharadin) improved overall survival (OS) by 30% and time to first skeletal-related event (SRE) by 39% compared with placebo, according to phase III data presented at the 2011 European Multidisciplinary Cancer Congress in Stockholm, Sweden.
Other important findings in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial included normalization of alkaline phosphatase in 33% of men who received radium-223 versus 1% of the placebo group and a 49% improvement in time to PSA progression with radium-223.
"This is the first drug targeted to bone metastases in prostate cancer that has been shown to improve survival. Other drugs targeted to the bone [zoledronic acid and denosumab] treat symptoms. If approved, this drug is likely to become standard of care," said study author Chris Parker, MD, consultant clinical oncologist at the Royal Marsden Hospital in London.
Further, "Fewer hits are needed with the alpha emitter, whereas thousands of hits are needed with beta emitters," Dr. Parker explained.
ALSYMPCA was a randomized, double-blind, placebo-controlled international study comparing radium-223 plus current standard of care versus placebo plus current standard of care in castration-resistant prostate cancer patients with symptomatic bone metastasis. The study enrolled 992 patients from 19 countries who had at least two bone lesions on scintigraphy.
The study was initiated in 2008 by Algeta ASA and was halted at a pre-planned interim analysis in June 2011, due to the robust benefits of radium-223. At that time, patients in the placebo arm were offered treatment with radium-223. Radium-223 is now being developed by Bayer.
Median survival was 14 months in men treated with radium-223 versus 11.2 months for placebo (p=.00185); median time to first SRE was 13.4 months versus 8.4 months, respectively (p=.00046).
Non-hematologic adverse events occurring in at least 15% of patients were bone pain (43% with radium-223 vs. 58% for placebo); nausea (34% vs. 32%, respectively); diarrhea (22% vs. 13%); constipation (18% of both groups), and vomiting (17% vs. 13%). Grade 3 and 4 bone pain occurred in 18% of those randomized to radium-223 compared with 23% of the placebo group.
Dr. Parker said that he hopes radium-223 will gain regulatory approval for bone metastasis in advanced prostate cancer soon. He said that further trials might look at this drug in combination with other drugs used to treat castration-resistant disease and also at radium-223 given earlier in the course of the disease. In addition, he suggested that radium-223 might be useful in other primary cancers that spread to the bone, but said that studies are needed for validation.
Putting these findings in context, Oliver Sartor, MD, professor of medicine at Tulane School of Medicine, New Orleans, said that radium-223 is a new class of agent that meets the ultimate endpoint criterion of improving OS as well as preventing SREs.
In a study of denosumab versus placebo, presented at the 2011 AUA annual meeting and again at the European Multidisciplinary Cancer Congress, denosumab delayed the development of metastasis in men with non-metastatic castration-resistant prostate cancer, but did not alter overall progression-free survival (PFS), and OS was identical in both arms of that study.
"With no improvement in PFS or OS, delaying metastasis may not be an endpoint that passes muster at FDA," Dr. Sartor said, noting that the prospects for approval are brighter for radium-223, which did improve OS.
The trial was sponsored by Algeta ASA and Bayer Healthcare Pharmaceuticals. Dr. Parker has received honoraria as an advisory board member for Bayer. Dr. Sartor has served as a consultant to Algeta.