Pivotal data on radium in PCa published in NEJM

Data from a pivotal phase III trial of the radiotherapeutic agent radium Ra 223 dichloride (Xofigo) in castration-resistant prostate cancer (CRPC) patients have been published in the New England Journal of Medicine (2013; 369:213-23).

These data, from the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial, supported the FDA approval of Ra 223 injection in May. They were originally reported at the AUA annual meeting in San Diego.

“The publication of the ALSYMPCA data in the New England Journal of Medicine is important, as it will provide physicians with comprehensive data on this recently approved treatment that has demonstrated overall survival in men with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease,” explained North American principal investigator Oliver Sartor, MD, of the Tulane Cancer Center, New Orleans.

The ALSYMPCA trial was a phase III, randomized, double-blind, placebo-controlled international study of Ra 223 plus best standard of care versus placebo plus best standard of care in patients with CRPC, symptomatic bone metastases, and no known visceral metastatic disease. The study treatment consisted of up to six intravenous injections of Ra 223 or placebo each separated by an interval of 4 weeks.

Ra 223 significantly improved overall survival in the overall study population at the pre-specified interim analysis (HR=0.695, 95% CI: 0.552-0.875; p=.00185); median overall survival was 14 months with Ra 223 plus best standard of care (95% CI: 12.1-15.8) versus 11.2 months with placebo plus best standard of care (95% CI: 9.0-13.2). These findings were supported by an exploratory analysis performed before patient crossover with an additional 214 events in which Ra 223 showed improvement in overall survival (HR=0.695, [95% CI 0.581-0.832]); median overall survival was 14.9 months in the Ra 223 arm (95% CI: 13.9-16.1) versus 11.3 months in the placebo arm (95% CI: 10.4-12.8).

An alpha emitter, Ra 223 mimics calcium and homes in on places where tumors have formed in the bones, and it is potent enough to damage cancer cells’ DNA in “a single knockout,” said Neha Vapiwala, MD, of the University of Pennsylvania, Philadelphia and lead author of an article accompanying the study results (N Engl J Med 2013; 369:276-8).

“The real-world applicability of this new therapy is undeniable,” Dr. Vapiwala said. “The addition to our armamentarium of this well-tolerated, bone-targeted therapy that helps to not only relieve symptoms but also extend lives is an incredibly important development for the 30,000 men who are facing death from prostate cancer each year, and for all of the individuals who care for them.

“It is also a seminal event in the realm of alpha-emitter therapy, opening a new door for more research into this class of agents that has great potential in other areas of oncology.”

Dr. Sartor reports receiving consulting fees from Aragon, Astellas, Bavarian Nordic, Bellicum, Dendreon, Medivation, OncoGeneX, and Pfizer, consulting fees and grant support through his institution from Johnson & Johnson and Sanofi-Aventis, and grant support through his institution from Algeta, Bayer, and Takeda.

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