Radium-223 should be considered as a treatment option for patients with castration-resistant prostate cancer and symptomatic bone metastases, according to a study published in the June issue of the Lancet Oncology.
Skeletal events are vital to prevent and delay in managing patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) is a calcium mimetic and its efficacy and safety were assessed in a phase three multinational study known as ALSYMPCA. During the study, radium-223 plus best standard of care was compared to a placebo plus standard of care in patients with castration-resistant prostate cancer and bone metastases. The results led to the FDA approval of radium-223 for treating patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastases.
Lead author Oliver Sartor, MD, of Tulane Cancer Center in New Orleans, and colleagues offer secondary endpoint data from ALSYMPCA and post-hoc analyses in their study to further validate the effect of radium-223 on this patient cohort.
During the randomized trial, 921 patients with symptomatic-resistant prostate cancer with two or more bone metastases and no known visceral metastases who were receiving best standard of care were enrolled in the study. Patients were stratified as followed: those who had previously used docetaxel, baseline total alkaline phosphatase level and current bisphosphonate use.
The participants were assigned randomly to receiver either six intravenous injections of radium-223 or a matching placebo. One injection was given every four weeks. The researchers focused on the study’s secondary endpoint, which was time to first symptomatic skeletal event. Moreover, this was defined as the use of external beam radiation to relieve bone pain, occurrence of a new symptomatic pathological fracture, occurrence of spinal cord compression or tumor-related othropeadic surgical intervention.
Of the participants, 67 percent were randomly assigned to receive radium-223 and 33 percent were assigned to receive the placebo. Symptomatic skeletal events were found in 202 of the 614 patients in the radium-223 group and 116 of the 307 patients in the placebo group. The time to first symptomatic skeletal event was longer with radium-223 than with the placebo, with a median of 15 months versus nine months, respectively.
The researchers found that the risks of external beam radiation therapy for bone pain and spinal cord compression were reduced with radium-233 compared with the placebo. Radium-223 treatment did not seem to significantly reduce the risk of symptomatic pathological bone fracture or the need for tumor-relate orthopaedic surgical intervention.
“As overall survival was significantly increased by radium-223 compared with placebo in ALSYMPCA, these results together identify radium-223 as an agent that increases overall survival and has the added clinical benefit of decreasing the risk of symptomatic skeletal events associated with skeletal disease progression when compared with placebo,” wrote Sartor and colleagues.
The authors added: “This significant effect of radium-223 on symptomatic skeletal events, coupled with the positive effect on overall survival and highly favourable safety profile, further establishes the clinical benefits of radium-223 and provides valuable information to guide treatment decisions for patients with metastatic castration-resistant prostate cancer.”