was PSA progression (confirmed 25% increase over the patient's baseline/nadir) together with protocol-defined radiographic progression and symptomatic or clinical progression. Patients with prior ketoconazole treatment for prostate cancer were excluded from this study. The primary efficacy endpoint was overall survival.
The median age of enrolled patients was 69 years (range 39-95). The number of patients treated with ZYTIGA by racial group was Caucasian 737 (93.2%), Black 28 (3.5%), Asian 11 (1.4%) and other 14 (1.8%). Eleven percent of patients enrolled had an ECOG performance score of 2; 70% had radiographic evidence of disease progression with or without PSA progression; 70% had received one prior cytotoxic chemotherapy and 30% received two. Liver metastasis was present in 11% of patients treated with ZYTIGA.
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; |
