The pre-specified interim analysis of overall survival revealed a statistically significant improvement in patients receiving Xofigo plus best standard of care compared with patients receiving placebo plus best standard of care. An exploratory updated overall survival analysis performed before patient crossover with an additional 214 events resulted in findings consistent with the interim analysis (Table 5).

Table 5: Overall Survival Results from the Phase 3 Clinical Trial *
Survival time is calculated as months from date of randomization to date of death from any cause. Subjects who are not deceased at time of analysis are censored on the last date subject was known to be alive or lost to follow-up.
†
p-value is from a log-rank test stratified by total ALP, current use of bisphosphonates, and prior use of docetaxel.
‡
Hazard ratio is from a Cox proportional hazards model adjusted for total ALP, current use of bisphosphonates, and prior use of docetaxel. Hazard ratio < 1 favors radium-223 dichloride.
 Xofigo
 Placebo
 
Interim Analysis
  
Subjects randomized
 541
 268
 
Number of deaths
 191 (35.3%)
 123 (45.9%)
 
Censored
 350 (64.7%)
 145 (54.1%)
 
Median survival (months)*

(95% CI)
 14.0

(12.1, 15.8)
 11.2

( 9.0, 13.2)
 
p-value†
 0.00185
 
Hazard ratio (95% CI)‡
 0.695 (0.552, 0.875)
 
 
Updated Analysis
 
Subjects randomized
 614
 307
 
Number of deaths
 333 (54.2%)
 195 (63.5%)
 
Censored
 281 (45.8%)
 112 (36.5%)
 
Median survival (months)*

(95% CI)
 14.9

(13.9, 16.1)
 11.3

(10.4, 12.8)
 
Hazard ratio (95% CI)‡
 0.695 (0.581, 0.832)
Survival time is calculated as months from date of randomization to date of death from any cause. Subjects who are not deceased at time of analysis are censored on the last date subject was known to be alive or lost to follow-up.
†
p-value is from a log-rank test stratified by total ALP, current use of bisphosphonates, and prior use of docetaxel.
‡
Hazard ratio is from a Cox proportional hazards model adjusted for total ALP, current use of bisphosphonates, and prior use of docetaxel. Hazard ratio < 1 favors radium-223 dichloride.

The Kaplan-Meier curves for overall survival based on the updated survival results are shown in Figure 1.

Figure 1: Kaplan-Meier Overall Survival Curves from the Phase 3 Clinical Trial

 The survival results were supported by a delay in the time to first SSE favoring the Xofigo arm. The majority of events consisted of external beam radiotherapy to bone metastases.

REFERENCES
1.
Radiation Emergency Medical Management. [REMM/National Library of Medicine Website.] http://www.remm.nlm.gov/int_contamination.htm#blockingagents
How Supplied/Storage and Handling
Xofigo (radium Ra 223 dichloride injection) is supplied in single-use vials containing 6 mL of solution at a concentration of 1,000 kBq/mL (27 microcurie/mL) with a total radioactivity of 6,000 kBq/vial (162 microcurie/vial) at the reference date (NDC 50419-208-01).

Store at room temperature,