Encouraging Long-Term Safety Data for Radium-223
San Francisco, CA—The safety and efficacy of radium Ra 223 dichloride (Xofigo, formerly Alpharadin) injection in men with castration-resistant prostate cancer (CRPC) and bone metastases have held up over the longer-term follow-up of the phase 3 Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial. Results of a study reported at the 2014 Genitourinary Cancers Symposium showed that at 1.5 years after the last injection of this therapy, minimal myelosuppression and minimal nonhematologic adverse events were reported, and there were no reports of cancers of concern, including acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), and primary bone cancer.
Lead investigator of the safety report, Sten Nilsson, MD, PhD, of the Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden, said these data support further evaluation of radium-223 in combination with other agents in this setting.
Last year, the US Food and Drug Administration approved radium-223 for the treatment of patients with CRPC and bone metastases based on the results of ALSYMPCA, showing that the drug significantly improved overall survival by 3.6 months compared with placebo (P <.001), with good tolerability.
ALSYMPCA enrolled 921 patients with CRPC and at least 2 symptomatic bone metastases. Patients with visceral metastases were excluded. Patients had received docetaxel or were not candidates for treatment with docetaxel, and were randomized in a 2:1 ratio to radium-223 (6 injections at 4-week intervals) or to placebo.
Of the 921 patients included, 574 entered 3-year follow-up (radium-223, N = 406; placebo, N = 168). Withdrawals from the 3-year follow-up included 322 (79%) patients in the radium-223 group and 144 (86%) patients in the placebo group. Death was the most common reason for withdrawal.
The median duration of follow-up was 10.4 months for radium-223 and 7.6 months for placebo. Only 20 patients (16 in the active group and 4 in the placebo group) completed the 3-year follow-up.
Only adverse events considered treatment-related were reported in this safety evaluation. The incidence of myelosuppression was <3% in patients receiving radium-223. No grade 3 or 4 nonhematologic treatment-related adverse events were reported with this agent, with the exception of 1 pathological fracture.
There were no reports of AML, MDS, or primary bone cancer. A total of 5 cancers in other organs were reported—2 in the active group and 3 in the placebo group.