News
Radium-223 dichloride, an alpha-particle–emitting radioactive agent, has been approved for treating men with castration-resistant prostate cancer that has spread to the bones, the Food and Drug Administration announced on May 15.
The agent "binds with minerals in the bone to deliver radiation directly to bone tumors," Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, noted in the statement.
Dr. Richard Pazdur
Ra-223 is the second drug for prostate cancer approved by the FDA in the last year that has been shown to extend the survival of men with metastatic prostate cancer, Dr. Pazdur noted. Enzalutamide (Xtandi), an androgen receptor inhibitor, was approved in August 2012 for treating men with metastatic castration-resistant prostate cancer who were previously treated with docetaxel.
Approval of the radium-223 treatment, which will be marketed as Xofigo by Bayer Pharmaceuticals, was based on a phase III study of men with symptomatic castration-resistant prostate cancer with symptomatic bone metastases, and no other metastases, randomized to treatment with radium 233 (541 men) every 4 weeks for six cycles or placebo (268 men). All patients received best standard of care, which included external-beam radiation therapy, corticosteroids, antiandrogens, estrogens, estramustine, or ketoconazole.
In an interim analysis, overall survival, the primary endpoint, was a median of 14 months among those in the radiotherapy arm, compared with 11.2 months among those on placebo, a highly statistically significant improvement, with a hazard ratio of 0.695. An updated exploratory analysis conducted later in the trial "confirmed Xofigo’s ability to extend overall survival," the FDA statement noted.
(The prescribing information states that in the updated analysis, median survival was 14.9 months vs. 11.3 months among those on placebo, with a hazard ratio of 0.695).
The most common side effects reported during clinical trials in men receiving the treatment, in 10% or more of patients, were nausea, diarrhea, vomiting and peripheral edema. The most common laboratory abnormalities detected, in 10% or more of patients, were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia.
Xofigo comes in a solution and is administered at 4-week intervals for six injection cycles; it is slowly administered intravenously over 1 minute. Safety and efficacy of more than six injections has not been studied, according to the prescribing information.