Scientific Publications by FDA Staff

Clin Cancer Res 2014 Jan 1;20(1):9-14

Radium Ra 223 dichloride injection: U.S. Food and Drug Administration Drug Approval Summary.

Kluetz PG, Pierce W, Maher VE, Zhang H, Tang S, Song P, Liu Q, Haber MT, Leutzinger EE, Al-Hakim A, Chen W, Palmby T, Alebachew E, Sridhara R, Ibrahim A, Justice R, Pazdur R

On May 15, 2013, the U.S. Food and Drug Administration approved radium Ra 223 dichloride (Xofigo(R) Injection, Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceral metastatic disease. The FDA review was based on clinical trial BC1-06, which randomly allocated patients (2:1) to either radium Ra 223 dichloride (Ra-223) plus best standard of care (BSoC) or placebo plus BSoC. The primary endpoint was overall survival (OS) with a key secondary endpoint of time to first symptomatic skeletal event (SSE). A statistically significant improvement in OS was demonstrated [HR 0.70 (95% CI: 0.55, 0.88), p = 0.0019]. At the pre-specified interim analysis, the median OS was 14.0 and 11.2 months in the Ra-223 and placebo arms, respectively. The improvement in OS was supported by a delay in time to first SSE favoring the Ra-223 arm. The most common (> 10%) adverse reactions in patients receiving Ra-223 were nausea, diarrhea, vomiting, and peripheral edema. The most common (> 10%) hematologic laboratory abnormalities were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. Radium-223 is the first alpha-emitting radiotherapeutic and the first radiopharmaceutical to demonstrate an OS advantage in metastatic prostate cancer.