Radium-223 Dichloride Prolongs Overall Survival in Men with Metastatic Prostate Cancer in Phase III ALSYMPCA Trial
In a trial (ALSYMPCA) reported in The New England Journal of Medicine, Chris Parker, MD, from Royal Marsden Hospital in Surrey, United Kingdom, and colleagues compared the alpha emitter radium-223 dichloride (Xofigo) with best standard of care in men with castration-resistant prostate cancer and bone metastases. Interim analysis showed that radium-223 dichloride treatment was associated with significantly prolonged overall survival, resulting in termination of the trial. An updated analysis, performed before crossover of the control group to radium-223 dichloride treatment, confirmed the overall survival advantage.
In this phase III double-blind trial, 921 patients who had received, were not eligible to receive, or declined docetaxel were randomized to receive six injections of radium-223 dichloride at a dose of 50 kBq/kg (n = 614) or matching placebo (n = 307) every 4 weeks, with all patients also receiving the best standard of care.
Overall Survival Analysis
A prespecified interim analysis involving 809 patients showed that radium-223 dichloride treatment was associated with significantly prolonged overall survival compared with placebo (median, 14.0 vs 11.2 months; hazard ratio [HR] = 0.70; P = .002). An updated analysis in all 921 patients, performed before crossover from placebo to radium-223 dichloride, showed a similar survival advantage for radium-223 dichloride treatment (median, 14.9 vs 11.3 months; HR = 0.70; P < .001). All main secondary efficacy endpoints supported the benefit of radium-223 dichloride, including significantly prolonged time to first symptomatic skeletal event (median, 15.6 vs 9.8 months; HR = 0.66; P < .001), time to increase in total alkaline phosphatase level (HR = 0.17, P < .001), and time to increase in prostate-specific antigen level (HR = 0.64, P < .001).
Safety
Radium-223 dichloride treatment was associated with lower rates of any adverse event (93% vs 96%), grade 3 or 4 adverse events (56% vs 62%), serious adverse events (47% vs 60%), and adverse events leading to study drug discontinuation (16% vs 21%). Hematologic adverse events of grade 3 or higher included anemia in 13% of patients in both groups, thrombocytopenia in 6.5% and 2%, and neutropenia in 3% and 1%. Grade 3 febrile neutropenia occurred in one patient in each group.
The investigators noted: “The treatment of prostate cancer has evolved since the trial began, with new data on the use of cabazitaxel [Jevtana Kit], abiraterone [Zytiga], and enzalutamide [Xtandi] in patients who have received docetaxel. The excellent safety profile of radium-223 and the non-overlapping mechanism of action make radium-223 potentially suitable for use either sequentially or in combination with these other agents.” A phase I/II trial of radium-223 dichloride combined with docetaxel in patients with castration-resistant prostate cancer and bone metastases is underway.
The trial was funded by Algeta and Bayer HealthCare Pharmaceuticals.
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