Radium-223 Dichloride Significantly Prolongs Time to First Symptomatic Skeletal Event in Patients With Castration-Resistant Prostate Cancer
In an article in The Lancet Oncology, Sartor et al report symptomatic skeletal event outcomes in the phase III ALSYMPCA trial, which was the study supporting the May 2013 approval of radium-233 dichloride (Xofigo) in patients with castration-resistant prostate cancer and bone metastases. They found that compared with placebo, radium-223 treatment was associated with significantly prolonged time to first symptomatic skeletal event, reduced risk of the need for external-beam radiation therapy for bone pain, and reduced risk of spinal cord compression.
Study Details
In this double-blind trial, 921 patients with symptomatic castration-resistant prostate cancer with at least two bone metastases and no known visceral metastases who had previously received or were unsuitable for docetaxel were randomly assigned 2:1 between June 2008 and February 2011 to receive six intravenous injections of radium-223 50 kBq/kg (n = 614) or placebo (n = 307), with one injection given every 4 weeks. The primary endpoint was overall survival, which was previously reported to be significantly prolonged with radium-223.
The current report is for the outcomes of time to first symptomatic skeletal event—defined as the use of external-beam radiation to relieve bone pain, occurrence of a new symptomatic pathologic fracture (vertebral or nonvertebral), or occurrence of spinal cord compression—and tumor-related orthopedic surgical intervention. All events had to be clinically apparent and were not assessed by periodic radiologic review.
Symptomatic skeletal events occurred in 202 patients (33%) in the radium-223 group and 116 patients (38%) in the placebo group. Overall, the need for external-beam radiation therapy for bone pain occurred in 32% of patients, symptomatic pathologic bone fracture in 6%, spinal cord compression in 5%, and tumor-related orthopedic surgical intervention in 2%.
Prolonged Time to First Event
Time to first symptomatic skeletal event was longer with radium-223 than with placebo (median, 15.6 vs 9.8 months, hazard ratio [HR] = 0.66, P = .00037). The number of patients requiring radium-223 treatment to prevent one symptomatic skeletal event during the first 6 months was 7.6 (95% confidence interval = 4.9–16.4).
Analysis by stratification factors showed significant prolongation of time to first event with radium-223 for patients with previous docetaxel (median, 13.5 vs 7.8 months, HR = 0.62, P = .00087), baseline alkaline phosphatase < 220 U/L (median 16.5 vs 10.2 months, HR = 0.64, P = .00297) or ≥ 220 U/L (median 14.1 vs 7.9 months, HR = 0.69, P = .0456), and patients with bisphosphonate use at study entry (median, 19.6 vs 10.2 months, HR = 0.49, P = .00048). Prolongation was not significant in patients with no previous docetaxel use (median, 17.0 vs 19.5 months, HR = 0.74, P = .12) or in patients with no bisphosphonate use at entry (median, 11.8 vs 8.4 months, HR = 0.77, P = .07)
Component Risks
Radium-223 treatment was associated with significantly reduced risk of external-beam radiation therapy for bone pain (30% vs 34%, HR 0.67, P = .00117) and risk of spinal cord compression (4% vs 7%, HR = 0.52, P = .03). Reductions in risk for symptomatic pathologic bone fracture (5% vs 7%, HR = 0.62, P = .10) and need for tumor-related orthopedic surgical intervention (2% vs 2%, HR = 0.72, P = .48) were not significant.
The investigators concluded, “Radium-223 should be considered as a treatment option for patients with castration-resistant prostate cancer and symptomatic bone metastases.”
Oliver Sartor, MD, of Tulane Cancer Center, Tulane Medical School, is the corresponding author for The Lancet Oncology article.
The study was funded by Algeta and Bayer HealthCare Pharmaceuticals. For full disclosures of the study authors, visit www.thelancet.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
