Interim data from a phase III trial of a novel radiation agent in men with castration-resistant prostate cancer (CRPC) showed the agent's efficacy to be significantly sufficient to bring the trial to a halt at a planned interim analysis so as to be able offer the agent to men in the placebo arm.
Data presented at the AUA annual meeting in Atlanta showed that radium-223 dichloride (Alpharadin) improved overall survival in patients with CRPC by 30.5%. Patients receiving treatment had a median survival of 14.9 months compared to 11.3 months in the placebo group (p=.0007).
"The hazard ratio at the time of interim analysis was 0.695 (p=.001885). This passed the threshold for early stoppage and prompted the committee to recommend that patients on placebo receive radium-223 in a crossover trial," said first author Oliver Sartor, MD, medical director of Tulane Cancer Center, New Orleans.
"I might point out that prior to this trial, there have been no agents targeting bone metastases that have demonstrated a prolongation in overall survival," said Dr. Sartor. "The rationale for treating patients with bone metastatic disease is clear. Bone metastases are a major cause of death, disability, and quality of life detriment."
Agent exhibits favorable safety profile
Dr. Sartor described the agent as an alpha emitter that binds, not to tumors, but to the calcium-enriched portion of newly laid bone. The alpha radiation penetrates but a short distance, perhaps 2 to 10 cell diameters, before decaying. This allows more specific targeting of the agent while minimizing damage to adjacent tissues.
The ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) randomized, double-blind, placebo-controlled trial involved more than 100 centers in 19 countries. It enrolled 921 patients with progressive, symptomatic CRPC with two or more bone metastases on scintigraphy but no known visceral metastasis. All patients received best standard of care but were docetaxel (Taxotere) ineligible, docetaxel intolerable, had failed docetaxel therapy, or had refused docetaxel therapy. Patients were randomized 2:1 to receive six intravenous injections at 50 kBq/kg of radium-223 every 4 weeks or placebo.
Radium-223 also showed benefits in measures of secondary outcomes. The agent slowed time to alkaline phosphatase (HR 0.163 [95% CI: 0.121, 0.221] p<.00001) and time to PSA progression (HR 0.671 [95% CI: 0.546, 0.826] p=.00015]). Radium-223 also produced a total alkaline phosphatase response (ie, 35% reduction) in 43% of patients compared to 3% of the placebo group and normalization of alkaline phosphatase in 33% of treated patients compared to 1% of the placebo group.
Radium-223 has been granted fast track designation by the FDA.
Dr. Sartor is a consultant/adviser for Algeta and receives honoraria from Bayer HealthCare. Several of his co-authors are consultant advisers for Algeta and/or employees of Bayer.