Trial Outcomes & Findings for Sorafenib as Adjuvant Treatment in the Prevention Of Recurrence of Hepatocellular Carcinoma (STORM) (NCT NCT00692770)

NCT ID: NCT00692770

Last Updated: 2018-08-08

Results Overview

Disease recurrence of HCC (intra or extra hepatic) was defined as the appearance of a new intrahepatic lesions fulfilling the American Association for the Study of Liver Diseases (AASLD) criteria of diagnosis of HCC or a new extra-hepatic lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.0. In addition to investigator assessment, all images were reviewed by an independent panel of radiologists. The calculation of the RFS was based on the independent evaluation of the scans. RFS was defined as the time from randomization to the first documented disease recurrence by independent radiological assessment or death due to any cause whichever occurred first. For subjects who had not recurred or died at the time of analysis, RFS was censored at their last date of evaluable scan before drop-out for any other reason than recurrence or death.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1114 participants
• Primary outcome timeframe: From randomization up to 4 years or until disease recurrence whichever came first
• Results posted on: 2018-08-08

Participant Flow

Participant recruitment period was between 15 August 2008 to 12 November 2010.

Of 1602 participants who were screened for inclusion in the study, 1114 were enrolled, and 1107 received treatment.

Participant milestones

Measure	Sorafenib (Nexavar, BAY43-9006) Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Placebo Participants received 2 tablets of placebo orally twice daily (BID)
Overall Study STARTED	556	558
Overall Study Participants Received Treatment	553	554
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	556	558

Reasons for withdrawal

Measure	Sorafenib (Nexavar, BAY43-9006) Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Placebo Participants received 2 tablets of placebo orally twice daily (BID)
Overall Study Protocol Violation	2	7
Overall Study Withdrawal by Subject	97	36
Overall Study Adverse Event	136	41
Overall Study Death	10	5
Overall Study Lost to Follow-up	7	3
Overall Study Non-compliant with study medication	11	5
Overall Study Progression by clinical judgment	2	3
Overall Study Physician decision not protocol driven	10	14
Overall Study Disease progression, recurrence/relapse	170	279
Overall Study Protocol driven decision point	3	7
Overall Study Completed all planned assessments	79	101
Overall Study Radiological and clinical progression	8	8
Overall Study Clinical endpoint reached	16	43
Overall Study Study terminated by sponsor	2	2
Overall Study Randomized but not treated	3	4

Baseline Characteristics

Sorafenib as Adjuvant Treatment in the Prevention Of Recurrence of Hepatocellular Carcinoma (STORM)

Baseline characteristics by cohort

Measure	Sorafenib (Nexavar, BAY43-9006) n=556 Participants Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Placebo n=558 Participants Participants received 2 tablets of placebo orally twice daily (BID)	Total n=1114 Participants Total of all reporting groups
Age, Continuous	58.1 Years STANDARD_DEVIATION 11.7 • n=5 Participants	58.7 Years STANDARD_DEVIATION 12.2 • n=7 Participants	58.4 Years STANDARD_DEVIATION 12.0 • n=5 Participants
Age, Customized <18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized Between 18 and 65 years	383 Participants n=5 Participants	361 Participants n=7 Participants	744 Participants n=5 Participants
Age, Customized >=65 years	173 Participants n=5 Participants	197 Participants n=7 Participants	370 Participants n=5 Participants
Sex: Female, Male Female	105 Participants n=5 Participants	97 Participants n=7 Participants	202 Participants n=5 Participants
Sex: Female, Male Male	451 Participants n=5 Participants	461 Participants n=7 Participants	912 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization up to 4 years or until disease recurrence whichever came first

Population: Full analysis set (FAS) included participants who were randomized to study treatments.

Disease recurrence of HCC (intra or extra hepatic) was defined as the appearance of a new intrahepatic lesions fulfilling the American Association for the Study of Liver Diseases (AASLD) criteria of diagnosis of HCC or a new extra-hepatic lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.0. In addition to investigator assessment, all images were reviewed by an independent panel of radiologists. The calculation of the RFS was based on the independent evaluation of the scans. RFS was defined as the time from randomization to the first documented disease recurrence by independent radiological assessment or death due to any cause whichever occurred first. For subjects who had not recurred or died at the time of analysis, RFS was censored at their last date of evaluable scan before drop-out for any other reason than recurrence or death.

Outcome measures

Measure	Sorafenib (Nexavar, BAY43-9006) n=556 Participants Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Placebo n=558 Participants Participants received 2 tablets of placebo orally twice daily (BID)
Recurrence Free Survival (RFS) by Independent Assessment	1014 Days Interval 839.0 to 1339.0	1026 Days Interval 841.0 to 1185.0

SECONDARY outcome

Timeframe: From randomization up to 4 years or until disease recurrence whichever came first

Population: FAS included participants who were randomized to study treatments.

TTR was defined as the time from randomization to the first documented disease recurrence by independent radiological assessment. For subjects who had not recurred at the time of analysis, TTR was censored at their last date of evaluable scan before withdrawal for any other reason than recurrence. "NA" in the reported data indicates values could not be estimated due to censored data.

Outcome measures

Measure	Sorafenib (Nexavar, BAY43-9006) n=556 Participants Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Placebo n=558 Participants Participants received 2 tablets of placebo orally twice daily (BID)
Time to Recurrence (TTR) by Independent Assessment	1172 Days Interval 924.0 to Value cannot be estimated due to censored data.	1089 Days Interval 923.0 to 1260.0

SECONDARY outcome

Timeframe: From randomization of the first subject until 4 years later.

Population: FAS included participants who were randomized to study treatments.

OS was defined as the time from randomization to date of death due to any cause. OS for subjects alive at the time of analysis was censored at their last date of contact. "NA" in the reported data indicates values could not be estimated due to censored data.

Outcome measures

Measure	Sorafenib (Nexavar, BAY43-9006) n=556 Participants Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Placebo n=558 Participants Participants received 2 tablets of placebo orally twice daily (BID)
Overall Survival (OS)	NA Days "NA" in the reported data indicates values could not be estimated due to censored data.	NA Days "NA" in the reported data indicates values could not be estimated due to censored data.

OTHER_PRE_SPECIFIED outcome

Timeframe: Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit

Population: FAS included participants who were randomized to study treatments.

The EQ-5D is a generic quality of life preference based on a validated instrument used in cancer and in general population, with 2 parts: Index and Visual Analogue Scale. The EQ-5D Index is a descriptive system of the following health dimensions: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression. Subjects were asked to choose any one of the 3 response levels for each dimension: no problems, some problems, and severe problems. The 5 health dimensions were summarized into a single score, the EQ-5D Index score which ranged from -0.59 to 1 with higher scores representing better health states (0=death, 1= perfect health, and -0.59=a health state worse than death). A change of at least 0.10 to 0.12 points was considered a minimally important difference using Eastern Cooperative Oncology Group Performance Status as the anchor. The results on the Analysis of covariance of timeadjusted Area under curve for the EQ-5D index score were reported.

Outcome measures

Measure	Sorafenib (Nexavar, BAY43-9006) n=556 Participants Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Placebo n=558 Participants Participants received 2 tablets of placebo orally twice daily (BID)
Patient Reported Outcomes: Euroqol-5 Dimensions (EQ-5D) - Index Score	0.827 Unit on a scale Interval 0.804 to 0.85	0.866 Unit on a scale Interval 0.843 to 0.888

OTHER_PRE_SPECIFIED outcome

Timeframe: Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit

Population: FAS included participants who were randomized to study treatments.

The EQ-5D is a generic quality of life preference based on a validated instrument used in cancer and in general population, with 2 parts: Index and Visual Analogue Scale. The EQ-5D VAS is a measure that represents health status as a single value. It is a 20-centimetre vertical graduated visual analogue scale with scores that ranged from 0 (worst imaginable health state) to 100 (best imaginable health state). The respondent rated his/her current health state by drawing a line from the box marked 'your own health state today' to the appropriate point on the EQ-5D VAS. A 3-digit number (including leading zeros) was read off the scale from the point where the respondent's line crossed the scale, which was the EQ-5D VAS score. A change of at least 7 points on the VAS was considered as minimally important. The results on the ANCOVA analysis of time-adjusted AUC for the EQ-5D VAS score were reported.

Outcome measures

Measure	Sorafenib (Nexavar, BAY43-9006) n=556 Participants Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Placebo n=558 Participants Participants received 2 tablets of placebo orally twice daily (BID)
Patient Reported Outcomes: Euroqol-5 Dimensions (EQ-5D) - Visual Analogue Scale (VAS) Score	77.203 Unit on a scale Interval 75.184 to 79.223	80.181 Unit on a scale Interval 78.212 to 82.151

OTHER_PRE_SPECIFIED outcome

Timeframe: Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit

Population: FAS included participants who were randomized to study treatments.

The FACT-HEP is a 45 item, self-administered, multi-dimensional, psychometrically sound questionnaire used extensively in oncology clinical trials. FACT-HEP consisted of five subscales: Physical Well-Being (PWB), Social Well-Being (SWB), Emotional Well-Being (EWB), Functional Well-Being (FWB), and Hepatobiliary Cancer Subscale (HCS). The PWB, FWB, SWB and EWB were summed to form the FACTGeneral (FACT-G) total score. The FACT-G and HCS scores were summed to form the FACT-HEP total score. FACT-HEP scores ranged from 0 to 180 and the higher scores represented a better quality of life. Subjects responded to each item on a 5-point Likert-type scale ranging from 0 (not at all) to 4 (very much). The minimally important difference (MID) for the FACT-Hep total score was in the range of 8 to 9. The results on the ANCOVA analysis of time-adjusted AUC for the FACT-HEP score were reported.

Outcome measures

Measure	Sorafenib (Nexavar, BAY43-9006) n=556 Participants Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Placebo n=558 Participants Participants received 2 tablets of placebo orally twice daily (BID)
Patient Reported Outcomes: Functional Assessment of Cancer Therapy (FACT)- Hepatobiliary Subscale (HEP) Score	138.7 Unit on a scale Interval 135.9 to 141.5	143.79 Unit on a scale Interval 141.1 to 146.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit

Population: FAS included participants who were randomized to study treatments.

The PWB, FWB, SWB and EWB were summed to form the FACT-G total score. Subjects responded to each item on a 5-point Likert-type scale ranging from 0 (not at all) to 4 (very much). FACT-G scores ranged from 0 to 108 and the higher scores represented a better quality of life. The MID for the FACT-G total score was in the range of 6 to 7. The results on the ANCOVA analysis of time-adjusted AUC for the FACT-G score were reported.

Outcome measures

Measure	Sorafenib (Nexavar, BAY43-9006) n=556 Participants Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Placebo n=558 Participants Participants received 2 tablets of placebo orally twice daily (BID)
Patient Reported Outcomes: Functional Assessment of Cancer Therapy (FACT)- General (G) Total Score	80.46 Unit on a scale Interval 78.6 to 82.3	82.95 Unit on a scale Interval 81.1 to 84.8

OTHER_PRE_SPECIFIED outcome

Timeframe: At Baseline

Population: Plasma biomarker analysis was done in 858 (77%) of the all enrolled subjects.

Biomarker was analyzed at baseline [i.e., before treatment] as a dichotomized variable based on median biomarker levels, and dichotomized into "high" and "low" groups using an optimal max chi cut-off approach - not per intervention. As such, results were analyzed according to this stratification. Max-chi square methodology was used to search for the optimal cut point for dichotomization of each plasma biomarker and Kaplan-Meier curves were generated using the optimal cut point for each possible association examined. These biomarker analyses were retrospective and exploratory and of signal generating nature only.

Outcome measures

Measure	Sorafenib (Nexavar, BAY43-9006) n=258 Participants Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Placebo n=600 Participants Participants received 2 tablets of placebo orally twice daily (BID)
The Correlation Between Plasma Biomarker Levels at Baseline With RFS to Determine Prognostic Value of Biomarkers - ANG-2	588 Days Interval 344.0 to 839.0	1260 Days Interval 1026.0 to Value cannot be estimated due to censored data.

OTHER_PRE_SPECIFIED outcome

Timeframe: At Baseline

Population: Plasma biomarker analysis was done in 858 (77%) of the all enrolled subjects.

Biomarker was analyzed at baseline [i.e., before treatment] as a dichotomized variable based on median biomarker levels, and dichotomized into "high" and "low" groups using an optimal max chi cut-off approach - not per intervention. As such, results were analyzed according to this stratification. Max-chi square methodology was used to search for the optimal cut point for dichotomization of each plasma biomarker and Kaplan-Meier curves were generated using the optimal cut point for each possible association examined. These biomarker analyses were retrospective and exploratory and of signal generating nature only.

Outcome measures

Measure	Sorafenib (Nexavar, BAY43-9006) n=333 Participants Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Placebo n=525 Participants Participants received 2 tablets of placebo orally twice daily (BID)
The Correlation Between Plasma Biomarker Levels at Baseline With RFS to Determine Prognostic Value of Biomarkers - AFP	668 Days Interval 420.0 to 924.0	1267 Days Interval 1094.0 to Value cannot be estimated due to censored data.

OTHER_PRE_SPECIFIED outcome

Timeframe: At Baseline

Population: Plasma biomarker analysis was done in 858 (77%) of the all enrolled subjects.

Biomarker was analyzed at baseline [i.e., before treatment] as a dichotomized variable based on median biomarker levels, and dichotomized into "high" and "low" groups using an optimal max chi cut-off approach - not per intervention. As such, results were analyzed according to this stratification. Max-chi square methodology was used to search for the optimal cut point for dichotomization of each plasma biomarker and Kaplan-Meier curves were generated using the optimal cut point for each possible association examined. These biomarker analyses were retrospective and exploratory and of signal generating nature only.

Outcome measures

Measure	Sorafenib (Nexavar, BAY43-9006) n=632 Participants Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Placebo n=226 Participants Participants received 2 tablets of placebo orally twice daily (BID)
The Correlation Between Plasma Biomarker Levels at Baseline With RFS to Determine Prognostic Value of Biomarkers - MET	841 Days Interval 675.0 to 1008.0	NA Days Interval 1262.0 to Value cannot be estimated due to censored data.

Adverse Events

Placebo

Serious events: 230 serious events

Other events: 360 other events

Deaths: 0 deaths

Sorafenib (Nexavar, BAY43-9006)

Serious events: 228 serious events

Other events: 522 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=548 participants at risk Subjects received 2 tablets of placebo orally twice daily.	Sorafenib (Nexavar, BAY43-9006) n=559 participants at risk Subjects received 2 tablets of Sorafenib \[2\*200 milligram (mg)\] orally twice daily.
Blood and lymphatic system disorders Anaemia	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Blood and lymphatic system disorders Neutropenia	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Blood and lymphatic system disorders Bone marrow failure	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Cardiac disorders Acute myocardial infarction	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Cardiac disorders Angina pectoris	0.36% 2/548 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Cardiac disorders Angina unstable	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Cardiac disorders Aortic valve stenosis	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Cardiac disorders Atrioventricular block complete	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Cardiac disorders Bradycardia	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Cardiac disorders Cardiac failure	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Cardiac disorders Cardiac failure congestive	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Cardiac disorders Coronary artery disease	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Cardiac disorders Myocardial infarction	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Cardiac disorders Myocardial ischaemia	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Cardiac disorders Left ventricular dysfunction	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Ear and labyrinth disorders Deafness	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 5 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Ear and labyrinth disorders Tinnitus	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 5 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Ear and labyrinth disorders Vertigo	0.36% 2/548 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Eye disorders Cataract	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.72% 4/559 • Number of events 6 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Eye disorders Retinal vein occlusion	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 4 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Abdominal pain	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.54% 3/559 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Abdominal pain upper	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Ascites	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.54% 3/559 • Number of events 4 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Crohn's disease	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Diaphragmatic hernia, obstructive	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Diarrhoea	0.36% 2/548 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Duodenitis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Enteritis	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Femoral hernia	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Gastritis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.72% 4/559 • Number of events 4 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Haematemesis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Impaired gastric emptying	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Inguinal hernia	0.55% 3/548 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 5 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Large intestine perforation	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.72% 4/559 • Number of events 6 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Pancreatitis	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Pancreatitis acute	0.36% 2/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Small intestinal obstruction	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Stomatitis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Umbilical hernia	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.36% 2/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Gastric volvulus	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Varices oesophageal	0.36% 2/548 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Gastric varices haemorrhage	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Abdominal hernia	0.36% 2/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Localised intraabdominal fluid collection	0.18% 1/548 • Number of events 5 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
General disorders Asthenia	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
General disorders Chest pain	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
General disorders Death	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
General disorders Drowning	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
General disorders Fatigue	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.54% 3/559 • Number of events 4 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
General disorders Multi-organ failure	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.54% 3/559 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
General disorders Pyrexia	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
General disorders Sudden cardiac death	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
General disorders Coronary artery restenosis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
General disorders Inflammation	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
General disorders Unevaluable event	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Bile duct stone	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Biliary fistula	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Cholangitis	0.36% 2/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Cholangitis acute	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Cholecystitis	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Hepatic failure	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Hepatic function abnormal	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.72% 4/559 • Number of events 9 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Hepatorenal syndrome	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Jaundice cholestatic	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 5 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Bile duct stenosis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Hepatic mass	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Biloma	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Hepatobiliary disorders Liver injury	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Appendicitis	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Bacteraemia	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Bronchitis	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.54% 3/559 • Number of events 4 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Cellulitis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Gastrointestinal infection	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Hepatitis B	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Hepatitis C	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Liver abscess	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Nasopharyngitis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Osteomyelitis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Peritonitis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Pneumonia	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Pulmonary tuberculosis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Pyelonephritis	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Pyelonephritis acute	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Sepsis	0.36% 2/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Superinfection	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Tuberculosis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Upper respiratory tract infection	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Urinary tract infection	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Urosepsis	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Rectal abscess	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Staphylococcal bacteraemia	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Biliary sepsis	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Acute hepatitis B	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Abdominal abscess	0.55% 3/548 • Number of events 4 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Lung infection	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Peritonitis bacterial	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Infected dermal cyst	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Infectious pleural effusion	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Accidental overdose	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Arterial injury	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Humerus fracture	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Incisional hernia	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Radius fracture	0.55% 3/548 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Spinal compression fracture	0.18% 1/548 • Number of events 4 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Sternal fracture	0.18% 1/548 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Tibia fracture	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Ulna fracture	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Vascular injury	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Wrist fracture	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.18% 1/548 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Face injury	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Brain contusion	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Wound evisceration	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Post procedural bile leak	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Pelvic fracture	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Limb crushing injury	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Injury, poisoning and procedural complications Toxicity to various agents	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Investigations Alanine aminotransferase increased	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Investigations Aspartate aminotransferase increased	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Investigations Lipase increased	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Investigations Liver function test abnormal	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Investigations Weight decreased	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Metabolism and nutrition disorders Dehydration	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Metabolism and nutrition disorders Diabetes mellitus	0.36% 2/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Metabolism and nutrition disorders Hypoglycaemia	0.36% 2/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Musculoskeletal and connective tissue disorders Back pain	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Musculoskeletal and connective tissue disorders Bone formation increased	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Musculoskeletal and connective tissue disorders Exostosis	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.18% 1/548 • Number of events 16 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.36% 2/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.18% 1/548 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign hepatic neoplasm	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.18% 1/548 • Number of events 5 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of liver	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal squamous cell carcinoma	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.36% 2/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.18% 1/548 • Number of events 4 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal adenocarcinoma	0.18% 1/548 • Number of events 4 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Schwannoma	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the hypopharynx	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.36% 2/548 • Number of events 4 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.72% 4/559 • Number of events 8 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Desmoid tumour	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.18% 1/548 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatobiliary neoplasm	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Nasopharyngeal cancer	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lip and/or oral cavity cancer	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm recurrence	0.36% 2/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Huerthle cell carcinoma	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oral papilloma	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	23.7% 130/548 • Number of events 154 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	14.7% 82/559 • Number of events 98 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Carotid artery thrombosis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 4 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Cerebellar haemorrhage	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Cerebral haemorrhage	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Cerebral infarction	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 4 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Cerebral ischaemia	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Cerebrovascular accident	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Encephalopathy	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.54% 3/559 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Guillain-Barre syndrome	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Haemorrhage intracranial	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Headache	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Hepatic encephalopathy	0.36% 2/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.54% 3/559 • Number of events 7 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Hypertensive encephalopathy	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Neuropathy peripheral	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Presyncope	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Spinal cord compression	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Spinal cord infarction	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Psychiatric disorders Alcohol abuse	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Psychiatric disorders Alcoholism	0.18% 1/548 • Number of events 4 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Psychiatric disorders Confusional state	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Renal and urinary disorders Calculus urinary	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Renal and urinary disorders Hydronephrosis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Renal and urinary disorders Nephrolithiasis	0.36% 2/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Renal and urinary disorders Nephrotic syndrome	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Renal and urinary disorders Renal colic	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Renal and urinary disorders Renal failure	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Renal and urinary disorders Renal failure acute	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Renal and urinary disorders Ureteric obstruction	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Renal and urinary disorders Urinary retention	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Renal and urinary disorders Diabetic nephropathy	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Laryngeal oedema	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.54% 3/559 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.36% 2/548 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.18% 1/548 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.73% 4/548 • Number of events 5 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Pulmonary granuloma	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Sinusitis noninfective	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Skin and subcutaneous tissue disorders Dermal cyst	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	1.8% 10/559 • Number of events 11 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Skin and subcutaneous tissue disorders Rash	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 3 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Skin and subcutaneous tissue disorders Telangiectasia	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Surgical and medical procedures Incisional hernia repair	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Surgical and medical procedures Neoplasm prophylaxis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Surgical and medical procedures Removal of foreign body from gastrointestinal tract	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Vascular disorders Arteriovenous fistula	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.00% 0/559 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Vascular disorders Hypertension	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Vascular disorders Hypertensive crisis	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.36% 2/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Vascular disorders Peripheral vascular disorder	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Vascular disorders Inferior vena caval occlusion	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Vascular disorders Peripheral embolism	0.18% 1/548 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Vascular disorders Artery dissection	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 1 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/548 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	0.18% 1/559 • Number of events 2 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.

Other adverse events

Measure	Placebo n=548 participants at risk Subjects received 2 tablets of placebo orally twice daily.	Sorafenib (Nexavar, BAY43-9006) n=559 participants at risk Subjects received 2 tablets of Sorafenib \[2\*200 milligram (mg)\] orally twice daily.
Blood and lymphatic system disorders Thrombocytopenia	2.6% 14/548 • Number of events 97 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	5.2% 29/559 • Number of events 217 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Abdominal pain	8.4% 46/548 • Number of events 115 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	9.8% 55/559 • Number of events 156 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Abdominal pain upper	2.6% 14/548 • Number of events 36 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	5.0% 28/559 • Number of events 75 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Ascites	3.5% 19/548 • Number of events 67 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	7.0% 39/559 • Number of events 145 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Constipation	6.6% 36/548 • Number of events 122 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	7.3% 41/559 • Number of events 105 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Diarrhoea	11.7% 64/548 • Number of events 186 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	43.3% 242/559 • Number of events 1201 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Dyspepsia	5.5% 30/548 • Number of events 125 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	3.6% 20/559 • Number of events 112 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Gastrointestinal disorders Nausea	4.4% 24/548 • Number of events 45 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	8.9% 50/559 • Number of events 119 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
General disorders Fatigue	12.0% 66/548 • Number of events 300 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	14.8% 83/559 • Number of events 315 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
General disorders Pyrexia	4.4% 24/548 • Number of events 32 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	5.9% 33/559 • Number of events 39 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Infections and infestations Nasopharyngitis	6.9% 38/548 • Number of events 69 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	5.4% 30/559 • Number of events 66 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Investigations Alanine aminotransferase increased	6.9% 38/548 • Number of events 177 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	9.7% 54/559 • Number of events 251 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Investigations Aspartate aminotransferase increased	6.4% 35/548 • Number of events 188 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	9.1% 51/559 • Number of events 226 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Investigations Platelet count decreased	4.7% 26/548 • Number of events 202 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	8.6% 48/559 • Number of events 300 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Investigations Weight decreased	2.4% 13/548 • Number of events 41 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	10.7% 60/559 • Number of events 254 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Investigations Weight increased	7.7% 42/548 • Number of events 310 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	2.5% 14/559 • Number of events 68 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Metabolism and nutrition disorders Decreased appetite	3.3% 18/548 • Number of events 52 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	7.2% 40/559 • Number of events 104 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Musculoskeletal and connective tissue disorders Arthralgia	5.5% 30/548 • Number of events 139 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	6.1% 34/559 • Number of events 162 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Musculoskeletal and connective tissue disorders Back pain	6.8% 37/548 • Number of events 192 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	7.7% 43/559 • Number of events 152 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Nervous system disorders Headache	6.0% 33/548 • Number of events 108 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	7.2% 40/559 • Number of events 111 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Psychiatric disorders Insomnia	5.7% 31/548 • Number of events 178 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	4.3% 24/559 • Number of events 111 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Cough	8.0% 44/548 • Number of events 116 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	5.4% 30/559 • Number of events 76 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.55% 3/548 • Number of events 7 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	7.3% 41/559 • Number of events 133 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Skin and subcutaneous tissue disorders Alopecia	3.3% 18/548 • Number of events 65 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	33.5% 187/559 • Number of events 750 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	4.9% 27/548 • Number of events 139 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	69.8% 390/559 • Number of events 2196 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Skin and subcutaneous tissue disorders Pruritus	10.6% 58/548 • Number of events 263 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	8.4% 47/559 • Number of events 133 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Skin and subcutaneous tissue disorders Rash	8.2% 45/548 • Number of events 126 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	17.0% 95/559 • Number of events 296 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.
Vascular disorders Hypertension	11.9% 65/548 • Number of events 331 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.	25.4% 142/559 • Number of events 869 • From the date of signing informed consent up to 30 days post-treatment discontinuation In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group.

Additional Information

Therapeutic Area Head

BAYER

Email: clinical-trials-contact@bayerhealthcare.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60