A Multicenter, Open-Label, Phase 3 Trial to Compare the E... | NCT01761266

ID	Type	Description	Link
2012-002992-33	EudraCT Number

Name	Class
Merck Sharp & Dohme LLC	INDUSTRY

Label	Type	Description	Intervention Names
Lenvatinib	Active Comparator	Participants received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the participant's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.	Drug: Lenvatinib
Sorafenib	Active Comparator	Participants received sorafenib 400 mg tablets, orally, twice daily (BID) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.	Drug: Sorafenib

Name	Type	Description	Arm Group Labels	Other Names
Lenvatinib	Drug	12 mg (or 8 mg) once daily (QD) oral dosing.	Lenvatinib

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff.	From date of randomization until date of death from any cause (approximately up to 3.8 years)

Measure	Description	Time Frame
Progression Free Survival (PFS)	PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), or date of death, whichever occurred first. Disease progression was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. As planned, data for this secondary endpoint was collected and analyzed up to the primary completion date.

Measure	Description	Time Frame
Disease Control Rate (DCR)	DCR was defined as the percentage of participants with a best overall response of CR or PR, or stable disease (SD). Best overall response of SD must have been >=7 weeks after randomization. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference the baseline sum of the diameters of target lesions. SD was when a case does not qualify for either PR or PD and was new non-target lesions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. As planned, data for this pre-specified endpoint was collected and analyzed up to the primary completion date.

Eligibility Module

Eligibility Criteria

Participants must have confirmed diagnosis of unresectable HCC with any of the following criteria:
- Histologically or cytologically confirmed diagnosis of HCC.
- Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any etiology or with chronic hepatitis B or C infection criteria
At least one measurable target lesion according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) meeting the following criteria:

• Hepatic lesion
1. The lesion can be accurately measured in at least one dimension as >=1.0 centimeter (cm) (viable tumor for typical; and longest diameter for atypical), and
2. The lesion is suitable for repeat measurement.
  
  • Nonhepatic lesion
3. Lymph node (LN) lesion that measures at least one dimension as >=1.5 cm in the short axis, except for porta hepatis LN that measures >=2.0 cm in the short axis.
4. Non-nodal lesion that measures >=1.0 cm in the longest diameter Lesions previously treated with radiotherapy or locoregional therapy must show radiographic evidence of disease progression to be deemed a target lesion.
Participants categorized to stage B (not applicable for transarterial chemoembolization [TACE]) or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system.
Adequate bone marrow function, defined as:
- Absolute neutrophil count (ANC) >=1.5 X 10^9 per liter (/L)
- Hemoglobin (Hb) >=8.5 gram per deciliter (g/dL)
- Platelet count >=75 X 10^9/L.
Adequate liver function, defined as:
- Albumin >=2.8 g/dL
- Bilirubin less than or equal to (<=) 3.0 mg/dL
- Aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) <=5 X the upper limit of normal (ULN).
Adequate blood coagulation function, defined as international normalized ratio (INR) <=2.3.
Adequate renal function defined as creatinine clearance greater than (>) 40 milliliter per minute (mL/min) calculated per the Cockcroft and Gault formula.
Adequate pancreatic function, defined as amylase and lipase <=1.5 X ULN.
Adequately controlled blood pressure (BP) with up to 3 antihypertensive agents, defined as BP <=150/90 millimeters of mercury (mmHg) at Screening and no change in antihypertensive therapy within 1 week prior to the Cycle1/Day1.
Child-Pugh score A.
Eastern Cooperative Oncology Group (ECOG)- performance status (PS) 0 or 1.
Males or females aged at least 18 years (or any age >18 years as determined by country legislation) at the time of informed consent.
Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity of 25 International Units Per Liter (IU/L) or equivalent units of BhCG).

A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all with surgery at least 1 month before dosing).
Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the participant must agree to use a double barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.
Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). No sperm donation is allowed during the study period and for 30 days after study drug discontinuation.
Provide written informed consent.
Willing and able to comply with all aspects of the protocol.

Exclusion Criteria

Imaging findings for HCC corresponding to any of the following:
- HCC with >=50 percent liver occupation
- Clear invasion into the bile duct
- Portal vein invasion at the main portal branch (Vp4).
Participants who have received any systemic chemotherapy, including anti-vascular endothelial growth factor (VEGF) therapy, or any systemic investigational anticancer agents, including lenvatinib, for advanced/unresectable HCC. Note: Participants who have received local hepatic injection chemotherapy are eligible.
Participants who have received any anticancer therapy (including surgery, percutaneous ethanol injection, radio frequency ablation, transarterial [chemo] embolization, hepatic intra-arterial chemotherapy, biological, immunotherapy, hormonal, or radiotherapy) or any blood enhancing treatment (including blood transfusion, blood products, or agents that stimulate blood cell production, eg, granulocyte colony-stimulating factor [G-CSF]) within 28 days prior to randomization.
Participants who have not recovered from toxicities as a result of prior anticancer therapy, except alopecia and infertility. Recovery is defined as < Grade 2 severity per Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0).
Significant cardiovascular impairment: history of congestive heart failure > New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at Screening.
Prolongation of corrected QT interval (QTc) interval to >480 millisecond (ms)
Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib in the opinion of the investigator.
Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic INR monitoring, eg, warfarin or similar agents. Treatment with low molecular weight heparin and factor X inhibitors which do not require INR monitoring is permitted. Antiplatelet agents are prohibited throughout the study.
Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to randomization.
Gastric or esophageal varices that require interventional treatment within 28 days prior to randomization. Prophylaxis with pharmacologic therapy (eg, nonselective beta-blocker) is permitted.
Active malignancy (except for HCC or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 36 months.
Participants whose only target lesion(s) is in bone will be excluded.
Meningeal carcinomatosis.
Any history of or current brain or subdural metastases.
Participants having >1+ proteinuria on urine dipstick testing will undergo a 24-hour urine collection for quantitative assessment of proteinuria. Participants with a urine protein >=1g/24 hours will be ineligible.
Surgical arterial-portal venous shunt or arterial-venous shunt.
Any medical or other condition that in the opinion of the investigator would preclude the participant's participation in a clinical study.
Known intolerance to lenvatinib or sorafenib (or any of the excipients).
Human immunodeficiency virus (HIV) positive or active infection requiring treatment (except for hepatitis virus).
Any history of drug or alcohol dependency or abuse within the prior 6 months.
Any participant who cannot be evaluated by either triphasic liver computed tomography (CT) or triphasic liver Magnetic resonance imaging (MRI) because of allergy or other contraindication to both CT and MRI contrast agents.
Major surgery within 3 weeks prior to randomization or scheduled for surgery during the study.
Participants has had a liver transplant.

Facility	Status	City	State	ZIP	Country	Contacts
Facility # 1		Los Angeles	California		United States
Facility # 1

PubMed Identifier	Type	Citation	Retractions
38261521	Derived	Piscaglia F, Ikeda K, Cheng AL, Kudo M, Ikeda M, Breder V, Ryoo BY, Mody K, Ren M, Ramji Z, Sung MW. Association between treatment-emergent hypertension and survival with lenvatinib treatment for patients with hepatocellular carcinoma in the REFLECT study. Cancer. 2024 Apr 15;130(8):1281-1291. doi: 10.1002/cncr.35185. Epub 2024 Jan 23.
36341767

ID	Title	Description
FG000	Lenvatinib	Participants received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the participant's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Survival (OS)

OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff.

The FAS included all participants who were randomized.

Posted

Median

95% Confidence Interval

months

From date of randomization until date of death from any cause (approximately up to 3.8 years)

ID	Title	Description
OG000	Lenvatinib	Participants received lenvatinib capsules 12 mg based on the participant's body weight >=60 kg or 8 mg based on the participant's body weight <60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
OG001	Sorafenib	Participants received sorafenib 400 mg tablets, orally, twice daily (BID) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Units	Counts
Participants	OG000478 OG001476

Title

Denominators

Categories

Title	Measurements
	OG00013.6± 12.1(12.1 to 14.9) OG00112.3± 10.4(10.4 to 13.9)

Secondary

Progression Free Survival (PFS)

PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), or date of death, whichever occurred first. Disease progression was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. As planned, data for this secondary endpoint was collected and analyzed up to the primary completion date.

The FAS included all participants who were randomized.

Posted

Median

95% Confidence Interval

months

From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (approximately up to 3.8 years)

ID	Title	Description
OG000	Lenvatinib	Subjects received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the subject's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
OG001	Sorafenib	Participants received sorafenib 400 mg tablets, orally, twice daily (BID) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Secondary

Time to Progression (TTP)

TTP was defined as the time from the date of randomization to the date of first documentation of disease progression based on mRECIST. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. As planned, data for this secondary endpoint was collected and analyzed up to the primary completion date.

The FAS included all participants who were randomized.

Posted

Median

95% Confidence Interval

months

The time from the date of randomization to the date of first documentation of disease progression (approximately up to 3.8 years)

ID	Title	Description
OG000	Lenvatinib	Subjects received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the subject's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
OG001	Sorafenib	Participants received sorafenib 400 mg tablets, orally, twice daily (BID) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Secondary

Objective Response Rate (ORR)

ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on mRECIST. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference to the baseline sum of the diameters of target lesions. As planned, data for this secondary endpoint was collected and analyzed up to the primary completion date.

The FAS included all participants who were randomized.

Posted

Number

95% Confidence Interval

percentage of participants

From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (approximately up to 3.8 years)

ID	Title	Description
OG000	Lenvatinib	Subjects received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the subject's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
OG001	Sorafenib	Participants received sorafenib 400 mg tablets, orally, twice daily (BID) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Secondary

Time to Clinically Meaningful Worsening of Health Related Quality of Life (HRQoL) Assessed Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)

The EORTC QLQ-C30 included 30 questions comprising 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social) and 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnoea, appetite loss, insomnia, constipation, diarrhea and financial difficulties) and a single global health and QOL status score. Most questions used a 4-point scale (1=Not at all to 4=Very much); 2 questions used a 7-point scale (1= Very poor to 7=Excellent). All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem. As planned, data for this secondary endpoint was collected and analyzed up to the primary completion date.

The FAS included all participants who were randomized.

Posted

Median

95% Confidence Interval

months

Baseline up to Off-Treatment Visit (approximately up to 3.8 years)

ID	Title	Description
OG000	Lenvatinib	Subjects received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the subject's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Secondary

Time to Clinically Meaningful Worsening of HRQoL Assessed Using - EORTC QLQ- Hepatocellular Carcinoma Domain (HCC 18)

The EORTC QLQ-HCC-18 was an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30. EORTC QLQ-HCC 18 questionnaire included 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. Each individual item ranges from 1 to 4, where 1 = "not at all" and 4 = "very much." All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a functional scale represented a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represented a high QoL, but a high score for a symptom scale/item represented a high level of symptomatology/problem. As planned, data for this secondary endpoint was collected and analyzed up to the primary completion date.

The FAS included all participants who were randomized.

Posted

Median

95% Confidence Interval

months

Baseline up to Off-Treatment Visit (approximately up to 3.8 years)

ID	Title	Description
OG000	Lenvatinib	Subjects received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the subject's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
OG001	Sorafenib

Secondary

Time to Clinically Meaningful Worsening of HRQoL Assessed Using EuroQol Five Dimension Health Questionnaire (EQ-5D-3L)

The EuroQol five dimension health questionnaire (EQ-5D-3L) assesses quality of life along 5 dimensions. Participants rate 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 3-15 with "3" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. EQ-5D-3L also included an EQ visual analogue scale (VAS) that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Decrease from baseline in EQ-5D-3L signifies improvement. Total index EQ-5D-3L summary score was weighted with a range of -0.594 (worst) to 1.0 (best). EQ-5D-3L also included an EQ health utilities index (HUI) where 1.00 indicated perfect health while a score of 0.00 indicated death. As planned, data for this secondary endpoint was collected and analyzed up to the primary completion date.

The FAS included all participants who were randomized.

Posted

Median

95% Confidence Interval

months

Baseline up to Off-Treatment Visit (approximately up to 3.8 years)

ID	Title	Description
OG000	Lenvatinib	Subjects received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the subject's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Secondary

Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib

AUC was assessed on Cycle 1 Day 1, Cycle 2 Day 1 and Cycle 1 Day 15. Summarized data for all time points was reported. As planned, data for this secondary endpoint was collected and analyzed up to the primary completion date.

The pharmacokinetic (PK) analysis set included all participants who had received at least 1 dose of lenvatinib and had at least 1 quantifiable lenvatinib concentration.

Posted

Mean

Standard Deviation

nanogram*hour per milliliter (ng*h/mL)

Cycle 1 Day 1, Cycle 2 Day 1: pre-dose, 0.5-4 and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 2-12 hours post-dose (cycle length= 28 days)

ID	Title	Description
OG000	Lenvatinib 8 mg	Participants received lenvatinib capsules 12 mg based on the participant's body weight >=60 kg or 8 mg based on the participant's body weight <60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
OG001	Lenvatinib 12 mg	Participants received lenvatinib 12 mg capsules based on the participant's body weight (>=60 kg) at Baseline, orally, once daily in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Other Pre-specified

Disease Control Rate (DCR)

DCR was defined as the percentage of participants with a best overall response of CR or PR, or stable disease (SD). Best overall response of SD must have been >=7 weeks after randomization. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference the baseline sum of the diameters of target lesions. SD was when a case does not qualify for either PR or PD and was new non-target lesions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. As planned, data for this pre-specified endpoint was collected and analyzed up to the primary completion date.

The FAS included all participants who were randomized.

Posted

Number

95% Confidence Interval

percentage of participants

From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (approximately up to 3.8 years)

ID	Title	Description
OG000	Lenvatinib	Subjects received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the subject's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
OG001

Other Pre-specified

Clinical Benefit Rate (CBR)

CBR was defined as the percentage of participants with a best overall response of CR or PR or durable SD (duration of SD >=23 weeks after randomization). For participants whose best overall response (BOR) was SD, the duration of SD was defined as the time from the date of randomization to the first documented PD or death, whichever occurred first. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference the baseline sum of the diameters of target lesions. SD was when a case does not qualify for either PR or PD. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. As planned, data for this pre-specified endpoint was collected and analyzed up to the primary completion date.

The FAS included all participants who were randomized.

Posted

Number

95% Confidence Interval

percentage of participants

From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (approximately up to 3.8 years)

ID	Title	Description
OG000	Lenvatinib	Subjects received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the subject's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Other Pre-specified

Percent Change From Baseline in Serum Biomarker

The serum biomarkers analysed were angiopoietin-2 (ANG2), fibroblast growth factor 19 (FGF19), fibroblast growth factor 21 (FGF21), fibroblast growth factor 23 (FGF23) and vascular endothelial growth factor (VEGF) as blood serum biomarkers, and protein induced by vitamin K absence or antagonist-II (PIVKA-II) as a blood tumor marker in serum. As planned, data for this pre-specified endpoint was collected and analyzed up to the primary completion date.

The pharmacodynamics (PD) analysis set included all participants who received at least 1 dose of study drug and had evaluable PD data. Here "n" was participants who were evaluable for the outcome measure at given time points.

Posted

Median

Standard Deviation

percent change

Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1, Cycle 9 Day 1 and at the Off-Treatment Visit (approximately up to 3.8 years)

ID	Title	Description
OG000	Lenvatinib	Subjects received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the subject's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
OG001	Sorafenib	Participants received sorafenib 400 mg tablets, orally, twice daily (BID) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected476 at risk EG0010 events0 affected475 at risk
Anaemia vitamin B12 deficiency	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0012 events2 affected475 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Atrial flutter	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Heart valve stenosis	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Cataract	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Ascites	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00015 events12 affected476 at risk EG00115 events12 affected475 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0008 events8 affected476 at risk EG0012 events2 affected475 at risk
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0008 events7 affected476 at risk EG0017 events5 affected475 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0007 events6 affected476 at risk EG00111 events11 affected475 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0006 events6 affected476 at risk EG0010 events0 affected475 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0007 events6 affected476 at risk EG0015 events2 affected475 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0003 events3 affected476 at risk EG0011 events1 affected475 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0008 events2 affected476 at risk EG0010 events0 affected475 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0011 events1 affected475 at risk
Umbilical hernia	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected476 at risk EG0012 events2 affected475 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0014 events3 affected475 at risk
Intestinal haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0003 events1 affected476 at risk EG0010 events0 affected475 at risk
Varices oesophageal	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Colitis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Food poisoning	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Gastric perforation	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0012 events2 affected475 at risk
Haematochezia	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0012 events2 affected475 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0013 events2 affected475 at risk
Peritoneal haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0007 events7 affected476 at risk EG0014 events4 affected475 at risk
Portal vein thrombosis	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0006 events4 affected476 at risk EG0010 events0 affected475 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0006 events3 affected476 at risk EG0012 events2 affected475 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0004 events3 affected476 at risk EG0010 events0 affected475 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0007 events2 affected476 at risk EG0010 events0 affected475 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Acute hepatic failure	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Biliary dilatation	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0003 events1 affected476 at risk EG0010 events0 affected475 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0012 events2 affected475 at risk
Chronic hepatic failure	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected476 at risk EG0010 events0 affected475 at risk
Haemobilia	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0016 events5 affected475 at risk
Hepatic pain	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0004 events1 affected476 at risk EG0010 events0 affected475 at risk
Hepatorenal syndrome	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Hydrocholecystis	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Jaundice	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0014 events4 affected475 at risk
Liver injury	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Pneumonia	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0005 events5 affected476 at risk EG0017 events5 affected475 at risk
Cellulitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Gastroenteritis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0011 events1 affected475 at risk
Liver abscess	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0011 events1 affected475 at risk
Lung infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0011 events1 affected475 at risk
Urinary tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0003 events2 affected476 at risk EG0010 events0 affected475 at risk
Appendiceal abscess	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Bacteraemia	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Biliary tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0011 events1 affected475 at risk
Dengue fever	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Diverticulitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Escherichia sepsis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected476 at risk EG0010 events0 affected475 at risk
Gastrointestinal viral infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Groin abscess	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0011 events1 affected475 at risk
Infectious pleural effusion	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0011 events1 affected475 at risk
Lung abscess	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0011 events1 affected475 at risk
Perihepatic abscess	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0003 events1 affected476 at risk EG0010 events0 affected475 at risk
Periodontitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Pleural infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Postoperative abscess	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Scrotal infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Septic shock	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0012 events1 affected475 at risk
Tuberculosis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Urinary tract infection enterococcal	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Urosepsis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Acute sinusitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Aspergillus infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Bronchitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Device related infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Diabetic foot infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Ophthalmic herpes simplex	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Perineal abscess	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Pneumonia escherichia	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Intentional overdose	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Foreign body	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0012 events2 affected475 at risk
Subarachnoid haemorrhage	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0012 events1 affected475 at risk
Traumatic haematoma	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0012 events1 affected475 at risk
Blood bilirubin increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0008 events7 affected476 at risk EG0011 events1 affected475 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0011 events1 affected475 at risk
Alanine aminotransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Blood pressure decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Clostridium test positive	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Hepatic enzyme increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Neutrophil count decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Weight decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Haemoglobin decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0012 events2 affected475 at risk
Platelet count decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0015 events2 affected475 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG00012 events11 affected476 at risk EG0012 events2 affected475 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0003 events3 affected476 at risk EG0014 events2 affected475 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0003 events2 affected476 at risk EG0010 events0 affected475 at risk
Cachexia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected476 at risk EG0010 events0 affected475 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0011 events1 affected475 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0011 events1 affected475 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0015 events5 affected475 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0011 events1 affected475 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG00012 events11 affected476 at risk EG00114 events14 affected475 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0004 events3 affected476 at risk EG0014 events3 affected475 at risk
Liver carcinoma ruptured	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0003 events2 affected476 at risk EG0012 events1 affected475 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0003 events2 affected476 at risk EG0010 events0 affected475 at risk
Metastases to spine	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0011 events1 affected475 at risk
Infected neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Intracranial tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0012 events2 affected475 at risk
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Tumour necrosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0012 events2 affected475 at risk
Tumour rupture	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Malignant ascites	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Plasma cell myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG00035 events21 affected476 at risk EG0014 events3 affected475 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0005 events3 affected476 at risk EG0010 events0 affected475 at risk
Coma hepatic	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0004 events3 affected476 at risk EG0011 events1 affected475 at risk
Cerebral infarction	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0004 events2 affected476 at risk EG0010 events0 affected475 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0004 events2 affected476 at risk EG0011 events1 affected475 at risk
Headache	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Seizure	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0011 events1 affected475 at risk
Spinal cord compression	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Diplegia	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0011 events1 affected475 at risk
Disturbance in attention	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Dizziness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Facial paralysis	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Paralysis recurrent laryngeal nerve	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Posterior reversible encephalopathy syndrome	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Syncope	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected476 at risk EG0010 events0 affected475 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Basal ganglia haemorrhage	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Encephalopathy	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0012 events1 affected475 at risk
Loss of consciousness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Thrombotic cerebral infarction	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Major depression	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0005 events3 affected476 at risk EG0012 events2 affected475 at risk
Proteinuria	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0004 events4 affected476 at risk EG0010 events0 affected475 at risk
Renal failure	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Renal impairment	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0003 events2 affected476 at risk EG0013 events2 affected475 at risk
Haematuria	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
IgA nephropathy	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Renal tubular necrosis	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0006 events5 affected476 at risk EG0012 events2 affected475 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0004 events4 affected476 at risk EG0012 events2 affected475 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0004 events3 affected476 at risk EG0010 events0 affected475 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0004 events3 affected476 at risk EG0013 events3 affected475 at risk
Hepatopulmonary syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected476 at risk EG0011 events1 affected475 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Necrotising bronchiolitis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Non-cardiogenic pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Pulmonary infarction	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected476 at risk EG0010 events0 affected475 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0012 events2 affected475 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Intertrigo	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Seborrhoeic dermatitis	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0012 events2 affected475 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0013 events3 affected475 at risk
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Aortic dissection	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Circulatory collapse	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected476 at risk EG0010 events0 affected475 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Thrombophlebitis	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Hypotension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Shock	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Thrombophlebitis superficial	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Coronary artery disease	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected476 at risk EG0010 events0 affected475 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected476 at risk EG00112 events6 affected475 at risk
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0005 events1 affected476 at risk EG0010 events0 affected475 at risk
Myocardial infarction	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0005 events4 affected476 at risk EG0011 events1 affected475 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0011 events1 affected475 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0003 events3 affected476 at risk EG0010 events0 affected475 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Asthenia	General disorders	MedDRA 19.1	Systematic Assessment	EG0007 events7 affected476 at risk EG0011 events1 affected475 at risk
Pyrexia	General disorders	MedDRA 19.1	Systematic Assessment	EG0008 events7 affected476 at risk EG0016 events5 affected475 at risk
General physical health deterioration	General disorders	MedDRA 19.1	Systematic Assessment	EG0005 events5 affected476 at risk EG0014 events3 affected475 at risk
Oedema peripheral	General disorders	MedDRA 19.1	Systematic Assessment	EG0003 events3 affected476 at risk EG0011 events1 affected475 at risk
Fatigue	General disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0012 events2 affected475 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0012 events1 affected475 at risk
Death	General disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Generalised oedema	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Organ failure	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Peripheral swelling	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0012 events1 affected475 at risk
Sudden death	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0012 events2 affected475 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG00022 events14 affected476 at risk EG00111 events8 affected475 at risk
Sepsis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG00011 events7 affected476 at risk EG0014 events3 affected475 at risk
Peritonitis bacterial	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0003 events2 affected476 at risk EG0010 events0 affected475 at risk
Salmonellosis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0010 events0 affected475 at risk
Pneumothorax traumatic	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected476 at risk EG0015 events5 affected475 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0004 events4 affected476 at risk EG0010 events0 affected475 at risk
Confusional state	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0012 events2 affected475 at risk
Suicide attempt	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Cardiac failure	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Mantle cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk
Metastases to adrenals	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected476 at risk EG0011 events1 affected475 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected476 at risk EG0010 events0 affected475 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Ascites	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00082 events63 affected476 at risk EG00154 events39 affected475 at risk
Constipation	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00095 events76 affected476 at risk EG00162 events52 affected475 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG000406 events186 affected476 at risk EG001448 events223 affected475 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00040 events31 affected476 at risk EG00120 events18 affected475 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG000131 events90 affected476 at risk EG00194 events71 affected475 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00067 events45 affected476 at risk EG00176 events56 affected475 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG000110 events75 affected476 at risk EG00165 events37 affected475 at risk
Alanine aminotransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG00086 events53 affected476 at risk EG001108 events51 affected475 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG000128 events64 affected476 at risk EG001173 events80 affected475 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG00059 events32 affected476 at risk EG00140 events29 affected475 at risk
Blood bilirubin increased	Investigations	MedDRA 19.1	Systematic Assessment	EG000141 events67 affected476 at risk EG001128 events63 affected475 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 19.1	Systematic Assessment	EG00059 events33 affected476 at risk EG00162 events24 affected475 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG00060 events37 affected476 at risk EG00141 events27 affected475 at risk
Neutrophil count decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG000101 events41 affected476 at risk EG00121 events13 affected475 at risk
Platelet count decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG000260 events87 affected476 at risk EG001127 events59 affected475 at risk
Weight decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG000290 events149 affected476 at risk EG001182 events108 affected475 at risk
White blood cell count decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG000115 events47 affected476 at risk EG00155 events25 affected475 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG000269 events162 affected476 at risk EG001165 events126 affected475 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG00088 events43 affected476 at risk EG00156 events38 affected475 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG00052 events42 affected476 at risk EG00131 events20 affected475 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG00055 events48 affected476 at risk EG00130 events28 affected475 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG00056 events47 affected476 at risk EG00130 events25 affected475 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG00059 events38 affected476 at risk EG00132 events18 affected475 at risk
Headache	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG00057 events45 affected476 at risk EG00148 events39 affected475 at risk
Insomnia	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG00038 events33 affected476 at risk EG00134 events28 affected475 at risk
Proteinuria	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG000363 events117 affected476 at risk EG001125 events55 affected475 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG00054 events45 affected476 at risk EG00146 events37 affected475 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG000134 events113 affected476 at risk EG00169 events57 affected475 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG00035 events35 affected476 at risk EG00117 events15 affected475 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG00041 events34 affected476 at risk EG00146 events35 affected475 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG00059 events46 affected476 at risk EG001105 events77 affected475 at risk
Hypertension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG000419 events200 affected476 at risk EG001269 events147 affected475 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG00055 events35 affected476 at risk EG001104 events43 affected475 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG00081 events33 affected476 at risk EG00190 events28 affected475 at risk
Hypothyroidism	Endocrine disorders	MedDRA 19.1	Systematic Assessment	EG000104 events81 affected476 at risk EG0019 events8 affected475 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00057 events39 affected476 at risk EG00127 events24 affected475 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG000136 events82 affected476 at risk EG001111 events83 affected475 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00082 events58 affected476 at risk EG00159 events41 affected475 at risk
Asthenia	General disorders	MedDRA 19.1	Systematic Assessment	EG000122 events53 affected476 at risk EG00184 events48 affected475 at risk
Fatigue	General disorders	MedDRA 19.1	Systematic Assessment	EG000226 events141 affected476 at risk EG001170 events120 affected475 at risk
Oedema peripheral	General disorders	MedDRA 19.1	Systematic Assessment	EG000107 events67 affected476 at risk EG00145 events33 affected475 at risk
Pyrexia	General disorders	MedDRA 19.1	Systematic Assessment	EG00079 events63 affected476 at risk EG00174 events61 affected475 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG00016 events15 affected476 at risk EG001140 events120 affected475 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG000236 events128 affected476 at risk EG001614 events246 affected475 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00038 events32 affected476 at risk EG0018 events8 affected475 at risk
Dizziness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG00033 events29 affected476 at risk EG00122 events16 affected475 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG00039 events31 affected476 at risk EG00119 events17 affected475 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG00014 events9 affected476 at risk EG00152 events26 affected475 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG00037 events24 affected476 at risk EG0016 events6 affected475 at risk
Haematuria	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG00034 events25 affected476 at risk EG00111 events9 affected475 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG00026 events23 affected476 at risk EG00133 events25 affected475 at risk

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D008113	Liver Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D004066	Digestive System Diseases
D008107	Liver Diseases

ID	Term
D010671	Phenylurea Compounds
D014508	Urea
D000577	Amides
D009930	Organic Chemicals
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009536	Niacinamide
D009539	Nicotinic Acids
D000147	Acids, Heterocyclic
D006571	Heterocyclic Compounds
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring

ID	Title	Description
BG000	Lenvatinib	Participants received lenvatinib capsules 12 mg based on the participant's body weight >=60 kg or 8 mg based on the participant's body weight <60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
BG001	Sorafenib	Participants received sorafenib 400 mg tablets, orally, twice daily (BID) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Lenvatinib	Participants received lenvatinib capsules 12 mg based on the participant's body weight >=60 kg or 8 mg based on the participant's body weight <60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.	415	478	209	476	469	476
EG001	Sorafenib	Participants received sorafenib 400 mg tablets, orally, twice daily (BID) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.	402	476	149	475	469	475