Updated Phase III Data Show Radium-223 Significantly Improves Survival, Extends Time to First SRE

Christopher Parker, MD (right), speaking with a patient.

An updated analysis of the results of a phase III clinical trial showed that radium-223 dichloride (Xofigo) significantly improved overall survival (OS) and delayed time to the first skeletal-related event (SRE) in patients with metastatic prostate cancer, further confirming the results of an interim analysis and justifying the novel therapy’s FDA approval. These updated results were first presented at the 2013 Annual Meeting of the American Society of Clinical Oncology and recently published in The New England Journal of Medicine.

Radium-223 is a targeted alpha emitter that is able to bind to materials in the bone and emit radiation directly to bone tumors. Early clinical trials showed that it had a favorable safety profile and caused only minimal myelotoxicity. Prostate cancer metastasizes to the bone in approximately 90% of advanced cases of prostate cancer.

The interim analysis of the phase III, double-blind, randomized, multinational ALSYMPCA trial found that patients with castration-resistant prostate cancer (CRPC) who had at least two bone metastases had a median overall OS of 14.0 months compared with 11.2 months in patients who received a placebo, resulting in a 30% reduction in the risk of death (hazard ratio [HR] = 0.70; 95% CI, 0.55-0.88; two-sided P = .002).

In this updated analysis, the researchers found that the median OS in the radium-223 arm of the study was 14.9 months compared with 11.3 months in the control arm, further confirming the 30% reduction in the risk of death (HR = 0.70; 95% CI, 0.58-0.83; P <.001). Furthermore, the study found that radium-223 significantly delayed the time to first SRE, with the experimental arm experiencing a median time to first SRE of 15.6 months compared with 9.8 months in the placebo arm (HR = 0.66; 95% CI, 0.52- 0.83; P<.001).

“The quality of life and overall survival benefits observed with radium-223 represent real progress for patients, as bone metastases can be painful and lead to death in men with CRPC,” said Christopher Parker, MD, consultant in Clinical Oncology at The Royal Marsden Hospital and The Institute of Cancer Research in London and principal investigator of the trial, in a statement. “These data showing significantly improved overall survival, regardless of prior treatment with chemotherapy, add to our knowledge about the potential use and benefit of radium-223 in these patients.” The drug was approved by the FDA in May for the treatment of symptomatic metastatic CRPC that has spread to bones but not to other organs.

Since many other drugs have been recently approved for patients with CRPC, discovering the optimal combinations or sequences of these drugs is a very important question for oncologists today. Drugs such as sipuleucel-T (Provenge), abiraterone acetate (Zytiga), enzalutamide (Xtandi), docetaxel, and cabazitaxel (Jevtana) might work synergistically with radium-223, although these combinations still need to be explored.

“In the ALSYMPCA trial, patients were just stratified to have received or not received docetaxel or zoledronic acid, because when that study was done, these other therapies weren’t available,” said Neal Shore, MD, medical director at the Carolina Urologic Research Center in Myrtle Beach, South Carolina, in an interview. “So, I think it will be important to have investigator-initiated trials, and perhaps cooperative group studies or industry-sponsored studies, to give us a greater comfort level. It doesn’t strike me that there should be a challenge, intuitively, in giving these other therapeutics concomitantly, but we have to get the data, we have to do the studies, and that’s very important.”

Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium- 223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213-223.