.6 %; stage IV: 50.8 % vs. 46.9 %), and BCLC stage (stage B: 18.1 % vs. 16.8 %; stage C: 81.6 % vs. 83.2 %; stage D: < 1 % vs. 0 %).
The study was stopped after a planned interim analysis of OS had crossed the prespecified efficacy boundary. This OS analysis showed a statistically significant advantage for sorafenib over placebo for OS (HR: 0.69, p = 0.00058, see table 3).
There are limited data from this study in patients with Child Pugh B liver impairment and only one patient with Child Pugh C had been included.
Table 3: Efficacy results from study 3 (study 100554) in hepatocellular carcinoma
|
Efficacy Parameter
|
Sorafenib
(N=299)
|
Placebo
(N=303)
|
P-value
|
HR
(95% CI)
|
|
Overall Survival (OS) [median, weeks (95% CI)]
|
46.3
(40.9, 57.9)
|
34.4
(29.4, 39.4)
|
0.00058*
|
0.69
(0.55, 0.87)
|
|
Time to Progression (TTP) [median, weeks (95% CI)]**
|
24.0
(18.0, 30.0)
|
12.3
(11.7, 17.1)
|
0.000007
|
0.58
(0.45, 0.74)
|
CI=Confidence interval, HR=Hazard ratio (sorafenib over placebo)
* statistically significant as the p-value was below the prespecified O'Brien Fleming stopping boundary of 0.0077
** independent radiological review
A second Phase III, international, multi-centre, randomised, double blind, placebo-controlled study (Study 4, 11849) eva luated the clinical benefit of sorafenib in 226 patients with advanced hepatocellular carcinoma. This study, conducted in China, Korea and Taiwan confirmed the findings of Study 3 with respect to the favourable benefit-risk profile of sorafenib (HR (OS): 0.68, p = 0.01414).
In the pre-specified stratification factors (ECOG status, presence or absence of macroscopic vascular invasion and/or extrahepatic tumour spread) of both Study 3 and 4, the HR consistently favoured sorafenib over placebo. Exploratory subgroup analyses suggested that patients with distant metastases at baseline derived a less pronounced treatment effect.
Renal cell carcinoma
The safety and efficacy of sorafenib in the treatment of advanced renal cell carcinoma (RCC) were investigated in two clinical studies:
Study 1 (study 11213) was a Phase III, multi-centre, randomised, double blind, placebo-controlled study in 903 patients. Only patients with clear cell renal carcinoma and low and intermediate risk MSKCC (Memorial Sloan Kettering Cancer Center) were included. The primary endpoints were overall survival and progression-free survival (PFS).
Approximately half of the patients had an ECOG performance status of 0, and half of the patients were in the low risk MSKCC prognostic group.
PFS was eva luated by blinded independent radiological review using RECIST criteria. The PFS analysis was conducted at 342 events in 769 patients. The median PFS was 167 days for patients randomised to sorafe
