May 21, 2012 (Atlanta, Georgia) — In patients with bone metastases and castration-resistant prostate cancer (CRPC), radium-223 chloride (Ra-223) significantly prolonged overall survival and delayed time to first skeletal-related event (SRE), according to new findings from a phase 3 study.
Oliver Sartor, MD, from the Departments of Medicine and Urology at Tulane University School of Medicine in New Orleans, Louisiana, and colleagues presented the findings here in an oral podium session at the American Urological Association (AUA) 2012 Annual Scientific Meeting.
Dr. Sartor noted that Ra-223 is a first-in-class alpha-pharmaceutical that targets bone metastases. ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer), a phase 3, double-blind, randomized, multinational study, compared best standard of care plus Ra-223 or placebo in patients with bone metastases in CRPC.
"This is the first presentation of ALSYMPCA to the urologic community," Dr. Sartor told Medscape Medical News. "The data are roughly comparable in overall survival benefit to the other newer agents, but the toxicity profile appears excellent, and I personally envision that combinations of these newer agents will eventually be used," he said.
In the current study, patients had progressive, symptomatic CRPC with 2 or more bone metastases on scintigraphy and no known visceral metastases. All were receiving best standard of care and had previously received docetaxel, were docetaxel ineligible, or declined to receive docetaxel. Patients were randomly assigned 2:1 to receive 6 injections of Ra-223 every 4 weeks or matching placebo.
Of 924 patients, 615 were randomly assigned to Ra-223 and 307 were assigned to placebo between June 2008 and February 2011. On the basis of data from a planned interim analysis including 809 patients, Ra-223 significantly improved overall survival vs placebo (median overall survival duration, 14.0 vs 11.2 months, respectively; 2-sided P = .00185; hazard ratio [HR], 0.695; 95% confidence interval [CI], 0.552 - 0.875).
Time to first SRE was significantly delayed in the Ra-223 vs the placebo group (median time to SRE, 13.6 vs 8.4 months, respectively; P = .00046; HR, 0.610; 95% CI, 0.461 - 0.807).
Safety and tolerability of Ra-223 were favorable, with 1.8% and 0.8% of patients reporting grade 3/4 neutropenia and 4% and 2% of patients reporting thrombocytopenia in the Ra-223 and placebo groups, respectively. The percentage of patients reporting adverse events was lower in the Ra-223 group than the placebo group (adverse events of any grade in 88% vs 94% and grade 3/4 adverse events in 51% vs 59%, respectively).
"I think two things were surprising," Dr. Sartor said after his presentation. "One is that you have overall survival-positive [attitudes] — everyone moves into these types of trials with a sense of optimism, but until the data is there, you don't know. The other thing that was very nice to see was the lack of toxicity. There was a lot of concern about bone myelosuppression, but the truth is, we just didn't see it."
According to Dr. Sartor, an updated survival analysis will be presented at the upcoming American Society of Clinical Oncology (ASCO) annual meeting.
Session moderator Sam Chang, MD, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, noted that as a bone-targeted agent, this product is "unique in improving overall survival, which would make it a very important option and perhaps game changing."
However, Dr. Chang told Medscape Medical News that these results are demonstrated in a very select population. "This product targets bone turnover, and so those lesions that are most active are the ones most likely to be targeted — the problem is that we don't know when that highest level of activity is," he said. "Also, the study was in a very select population of patients, and at a very late stage. Can it be used earlier on? We don't know."
The study was supported by Algeta. Dr. Sartor reports that he is a consultant and investigator for Algeta and Bayer. Dr. Chang has disclosed no relevant financial relationships.
American Urological Association (AUA) 2012 Annual Scientific Meeting: Abstract #684. Presented May 20, 2012.