On May15, 2013, the U. S. Food and Drug Administration approved radium Ra 223 dichloride (Xofigo Injection, Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease. Xofigo is an alpha-particle emitting radiotherapeutic drug which mimics calcium and forms complexes with hydroxyapatite at areas of increased bone turnover, such as bone metastases.
The approval was based on a double-blind, randomized, placebo-controlled trial in patients with metastatic castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease. Patients were allocated 2:1 to Xofigo, 50 kBq/kg (1.35 microcurie/kg), intravenously, every 4 weeks for 6 cycles plus best standard of care (N=541) or to matching placebo plus best standard of care (N=268). Best standard of care included local radiotherapy, corticosteroids, anti-androgens, estrogens, estramustine or ketoconazole. All patients were to continue androgen deprivation therapy. The median age was 71 years, 94% were Caucasian, 86% had an ECOG performance status of 0-1, and 58% had received prior docetaxel. Fifty-four percent of patients used opiate and 44% used non-opiate pain medications. Overall survival (OS) was the primary endpoint.
At the pre-specified interim analysis, a statistically significant improvement in OS was demonstrated [HR 0.70 (95% CI: 0.55, 0.88), p = 0.00185]. The median OS was 14.0 and 11.2 months in the Xofigo and placebo arms, respectively. The improvement in OS was supported by a delay in time- to- first symptomatic skeletal event favoring the Xofigo arm.
The most common (> 10%) adverse reactions in patients receiving Xofigo were nausea, diarrhea, vomiting, and peripheral edema. The most common (> 10%) hematologic laboratory abnormalities were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. Two percent of patients on the Xofigo arm experienced bone marrow failure or ongoing pancytopenia. No patients on the placebo arm experienced bone marrow failure or pancytopenia.
The recommended dose and schedule for Xofigo is 50 kBq/kg (1.35 microcuries/kg) administered by slow intravenous injection over 1 minute every 4 weeks for 6 doses.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203971lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).