is, a total of 809 patients had been randomized 2:1 to receive Xofigo 50 kBq (1.35 microcurie)/kg intravenously every 4 weeks for 6 cycles (n = 541) plus best standard of care or matching placebo plus best standard of care (n = 268). Best standard of care included local EBRT, corticosteroids, antiandrogens, estrogens, estramustine or ketoconazole. Therapy was continued until unacceptable toxicity or initiation of cytotoxic chemotherapy, other systemic radioisotope, hemi-body EBRT or other investigational drug. Patients with Crohn’s disease, ulcerative colitis, prior hemibody radiation or untreated imminent spinal cord compression were excluded from the study. In patients with bone fractures, orthopedic stabilization was performed before starting or resuming treatment with Xofigo.
The following patient demographics and baseline disease characteristics were balanced between the arms. The median age was 71 (range 44-94) with a racial distribution of 94% Caucasian, 4% Asian, 2% Black and <1% Other. Patients were enrolled predominantly from Europe (85%) with 4% of patients enrolled from North America. ECOG performance status was 0-1 in 86% of patients. Eighty-five percent of patients had 6 or more bone scan lesions and of those 40% had > 20 lesions or a superscan. Opiate pain medications were used for cancer-related pain in 54% of patients, non-opiate pain medications in 44% of patients and no pain medications in 2% of patients. Patients were stratified by baseline ALP, bisphosphonate use, and prior docetaxel exposure. Prior bisphosphonates were used by 41% of patients and 58% had received prior docetaxel. During the treatment period, 83% of Xofigo patients and 82% of placebo patients received gonadotropin-releasing hormone agonists and 21% of Xofigo patients and 34% of placebo patients received concomitant antiandrogens. Use of systemic steroids (41%) and bisphosphonates (40%) was balanced between the arms.
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)
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