RADIUM-223 CHLORIDE FOR PROSTATE CANCER

June 12, 2012 (Miami Beach, Florida) — Radium-223 chloride significantly improved overall survival with very low toxicity in patients with castrate-resistant prostate cancer and bone metastases, researchers reported here at the SNM 2012 Annual Meeting.

The word "breakthrough" is seldom used when researchers are presenting their data, said presenting author Valerie Lewington, MD, from Guy's and St. Thomas' Hospital, London, United Kingdom, but that is just the word she used in a press conference for reporters covering the meeting.

"This is a completely new approach to the treatment of advanced prostate cancer," Dr. Lewington said. "It will treat multiple sites of metastases, no matter where they are in the body."

She presented updated data from the ALSYMPCA study, which was stopped early because of the benefit shown, as previously reported by Medscape Medical News. When the early results were originally presented, they were hailed by experts as practice-changing and suggested a new standard of care.

ALSYMPCA is an international double-blind randomized study of 922 patients with advanced castrate-resistant prostate cancer with 2 or more sites of bone metastases. Patients were treated with either radium-223 or saline (placebo). In addition, both groups received the best standard of care.

The patients had no known visceral disease and had received treatment with docetaxel or were unfit for docetaxel therapy.

The primary end point was overall survival.

Dr. Lewington reported that 615 patients received 6 intravenous injections of radium-223 (50 kBq/kg) every 4 weeks for 6 cycles, and 307 received matching placebo injections.

Radium-223 targets bone metastases with high linear energy transfer short-range (shorter than 100 µm) alpha-particles.

The researchers found that patients who received radium-223 survived, on average, 3.8 months longer than those who received placebo (median overall survival, 14.0 vs 11.2 months; P = .00185; hazard ratio [HR], 0.695; 95% confidence interval [CI], 0.552 to 0.875).

In addition, radium-223 delayed bone complications, particularly bone pain, by 5.5 months.

The agent was very well tolerated, Dr. Lewington noted.

"We feel this is a real breakthrough in the management of late-stage prostate cancer; it may offer a whole new standard of care for patients with advanced disease," she said.

"We can select patients in a very straightforward way with conventional bone scan. We hope that we will be able to use positron emission tomography/computed tomography and other nuclear medicine techniques to assess response to treatment."

Dr. Lewington told Medscape Medical News that she thinks radium-223 is a breakthrough because it is the first-in-class radiopharmaceutical to use the new therapeutic alpha-particle emitter.

"The thing about alpha-particles is that they travel a very short distance in bone; that means that they deliver an enormous amount of energy over a very short distance. This is what we think is contributing to the survival gain. Also, because the distance is so short, the drug doesn't irradiate the normal parts of the bone marrow. That's why the side effects, in terms of the blood stream and the bone marrow function, are much lower than we've seen with similar drugs that use beta-particle emitters and that stretch for a longer distance," Dr. Lewington said.

"As far as I know, it's the very first therapeutic application, on a large scale, of an alpha-particle treatment," she explained.

Peter Herscovitch, MD, chief of the Positron Emission Tomography Department at the National Institutes of Health in Bethesda, Maryland, commended the study in an interview with Medscape Medical News.

"It is an international study with a large number of subjects and a well-designed follow-up. It shows the impact of this new therapy in achieving a good outcome in a patient population that has been heretofore particularly difficult," Dr. Herscovitch said.

The study was supported by Algeta ASA. Dr. Lewington and Dr. Herscovitch have disclosed no relevant financial relationships.

SNM 2012 Annual Meeting: Abstract 222. Presented June 11, 2012.