A Phase III Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Overall Survival was defined as the time from date of starting treatment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.

Time frame: from randomization to death due to any cause until an average 7.2 months later up to the data cut-off date approximately 19 months after start of enrollment

Population: In this study the overall survival was measured for the ITT population from the date of randomization until the date of death due to any cause. For patients alive or lost to follow-up at the time of analysis, time to death was to be censored at their last date of follow-up, or at the data cut-off of 17 Oct 2006.

TTSP was defined as the time from randomization to the first documented symptomatic progression.

Time frame: from randomization to the first documented symptomatic progression until an average 4.8 months later up to the data cut-off date approximately 19 months after start of enrollment

Population: This analysis was for the ITT population. For subjects who had not progressed symptomatically at the time of interim analysis, TTSP was censored at the date of their last Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index (FHSI-8) questionnaire assessment.

The DC is defined as the number of subjects with a best response rating of complete response (CR), partial response (PR), or stable disease (SD) that is maintained at least 28 days from the first manifestation of that rating. Definitions: CR = disappearance of all clinical and radiological tumor lesions; PR = at least 30% decrease in sum of the longest diameters of tumor lesions; SD = neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease.

Time frame: time from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment

Population: In this study, the DC for the ITT population was determined by independent radiological review and also by investigator assessment (both by using response evaluation criteria in solid tumors \[RECIST\])

PRO is a disease-specific measure, developed as symptom-focused approach in HCC and measured by the response rates for the PWB and FWB subscales of the 45-item Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. The FACT-Hep response rate was based on the number of subjects who achieved the 8-point minimally important difference (MID) for this subscale. FACT-Hep total score ranges from 0 to 180, where the highest score represents a maximum achievable quality of life (QoL) value.

Time frame: from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment

Population: In this study, the PRO was a tertiary efficacy variable assessed for the ITT population at Cycle 3 day 1 or, for those discontinuing prior to that visit, at end of study. It was summarized as number of patients with change from baseline \<8 or ≥8 points for each treatment group up to the cutoff date of 17 Oct 2006

TTP was defined as the time from randomization to disease progression (radiological only). Subjects without tumor progression at the time of analysis were censored at their last date of tumor evaluation.

Time frame: from randomization to disease progression based on radiological assessment until an average 2.8 months later up to the data cut-off date approximately 19 months after start of enrollment

Population: The primary analysis of TTP for the ITT population was based on the independent radiological review for the interim analysis. The cut-off date chosen for the analysis of radiological progression events was 12 May 2006

The DC is defined as the number of subjects with a best response rating of CR, PR, or SD that is maintained at least 28 days from the first manifestation of that rating.

Time frame: from randomization to end of treatment up to the data cutoff date approximately 23 months after start of enrollment

Population: The disease control rate for the ITT population was determined by independent radiological review and also by investigator assessment (both by using response evaluation criteria in solid tumors (RECIST) up to the cutoff date of 09 Feb 2007

Overall Survival was defined as the time from date of starting treatment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.

Time frame: from randomization to death due to any cause until an average 8.5 months later up to the data cut-off date approximately 23 months after start of enrollment

Population: The OS data (ITT population) are descriptive only (no p-values) from the date of randomization to the date of death due to any cause. For patients alive at the time of analysis, time to death was censored at the date of last follow-up or at the data cutoff date of 09 Feb 2007 when subjects were given the option to crossover to sorafenib treatment

PRO is a disease-specific measure, developed as symptom-focused approach in HCC and measured by the response rates for the PWB and FWB subscales of the 45-item Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. The FACT-Hep response rate was based on the number of subjects who achieved the 8-point minimally important difference (MID) for this subscale. FACT-Hep total score ranges from 0 to 180, where the highest score represents a maximum achievable quality of life (QoL) value. At the cut-off date for this analysis, one more patient data has been gained.

Time frame: from randomization to end of treatment up to the data cutoff date approximately 23 months after start of enrollment

Population: In this study, the PRO was a tertiary efficacy variable assessed for the ITT population at Cycle 3 Day 1 or, for those discontinuing prior to that visit, at the end of study. It was summarized as number of patients with change from baseline \<8 to ≥8 points for each treatment group up to the cutoff date of 09 Feb 2007.

TTP was defined as the time from randomization to disease progression (radiological only). Subjects without tumor progression at the time of analysis were censored at their last date of tumor evaluation.

Time frame: from randomization to disease progression based on radiological assessment until an average 2.8 months later up to the data cut-off date approximately 23 months after start of enrollment

Population: The independent radiological review as initially scheduled for the interim analysis did not continue after 12 May 2006. The primary analysis of TTP for the ITT population after 12 May 2006 up to the cutoff date of 09 Feb 2007 was based on the Investigator radiological assessments

TTSP was defined as the time from randomization to the first documented symptomatic progression

Time frame: from randomization to the first documented symptomatic progression until an average 5.7 months later up to the data cut-off date approximately 23 months after start of enrollment

Population: For subjects (in the ITT population) who had not progressed symptomatically at the time of interim analysis, TTSP was censored at the date of last FACT FHSI-8 questionnaire assessment (upon an interim review by the Data Monitoring Committee on 09 Feb 2007), when the study was considered positive for its primary endpoint, OS, and was stopped early.