title: Radium Ra 223 dichloride injection: U.S. Food and Drug Administration drug approval summary.
abstract: On May 15, 2013, the U.S. Food and Drug Administration (FDA) approved radium Ra 223 dichloride (Ra-223; Xofigo 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 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% confidence interval, 0.55-0.88, P = 0.0019]. At the prespecified interim analysis, the median OS durations were 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. Ra-223 is the first α-emitting radiotherapeutic and the first radiopharmaceutical to demonstrate an OS advantage in metastatic prostate cancer.
authors.affiliation: Authors' Affiliations: Office of Hematology and Oncology Products, Office of Biostatistics, Office of Clinical Pharmacology, and Office of Pharmaceutical Science, Office of New Drug Quality Assessment, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Kluetz
authors.forename: William
authors.initials: W
authors.lastname: Pierce
authors.forename: V Ellen
authors.initials: VE
authors.lastname: Maher
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Shenghui
authors.initials: S
authors.lastname: Tang
authors.forename: Pengfei
authors.initials: P
authors.lastname: Song
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Martin T
authors.initials: MT
authors.lastname: Haber
authors.forename: Eldon E
authors.initials: EE
authors.lastname: Leutzinger
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Hakim
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Todd
authors.initials: T
authors.lastname: Palmby
authors.forename: Elleni
authors.initials: E
authors.lastname: Alebachew
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.forename: Amna
authors.initials: A
authors.lastname: Ibrahim
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000368:Aged; D000818:Animals; D001859:Bone Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D004311:Double-Blind Method; D017277:Drug Approval; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011868:Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D011883:Radium / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; C581106:radium Ra 223 dichloride; D011883:Radium