In a planned analysis conducted after 552 deaths were observed, 42% (333 of 797) of patients treated with ZYTIGA compared with 55% (219 of 398) of patients treated with placebo, had died. A statistically significant improvement in median overall survival was seen in patients treated with ZYTIGA (see Table 2).

Table 2: Overall survival of patients treated with either ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH agonists or prior orchiectomy
 
  ZYTIGA

(N=797)
 Placebo

(N=398)
 
Primary Survival Analysis

Deaths (%)
 333 (42%)
 219 (55%)
 
Median survival (months)

(95% CI)
 14.8 (14.1, 15.4)
 10.9 (10.2, 12.0)
 
p value a
 < 0.0001
 
Hazard ratio (95% CI) b
 0.646 (0.543, 0.768)
 
Updated Survival Analysis
    
Deaths (%)
 501 (63%)
 274 (69%)
 
Median survival (months)

(95% CI)
 15.8 (14.8, 17.0)
 11.2 (10.4, 13.1)
 
Hazard ratio (95% CI) b
 0.740 (0.638, 0.859)
 
aP-value is derived from a log-rank test stratified by ECOG performance status score (0-1 vs. 2), pain score (absent vs. present), number of prior chemotherapy regimens (1 vs. 2), and type of disease progression (PSA only vs. radiographic).

bHazard ratio is derived from a stratified proportional hazards model. Hazard ratio <1 favors ZYTIGA

At all eva luation time points after the initial few months of treatment, a higher proportion of patients treated with ZYTIGA remained alive, compared with the proportion of patients treated with placebo (see Figure 1).

Figure 1: Kaplan Meier survival curves of patients treated with either ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH agonists or prior orchiectomy

AA=ZYTIGA

Subgroup survival analyses showed a consistent survival benefit for treatment with ZYTIGA (see Figure 2).

Figure 2: Overall survival by subgroup: hazard ratio and 95% confidence interval

AA=ZYTIGA; BPI=Brief Pain Inventory; C.I.=confidence interval; ECOG=Eastern Cooperative Oncology Group performance score; HR=hazard ratio; NE=not eva luable

In addition to the observed improvement in overall survival, all secondary study endpoints favoured ZYTIGA and were statistically significant after adjusting for multiple testing as follows:

Patients receiving ZYTIGA demonstrated a significantly higher total PSA response rate (defined as a  50% reduction from baseline), compared with patients receiving placebo, 38% versus 10%, p < 0.0001.

The median time to PSA progression was 10.2 months for patients treated with ZYTIGA and 6.6 months for patients treated with placebo (HR=0.580; 95% CI: [0.462; 0.728], p < 0.0001).

The median radiographic progression-free survival was 5.6 months for patients treated with ZYTIGA and 3.6 months for patients who received placebo (HR=0.673; 95% CI: [0.585; 0.776], p < 0.0001).

Pain

The proportion of patients with pain palliation was statistically significant