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A Multicenter, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Versus Sorafenib in First-line Treatment of Participants With Unresectable Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT01761266
Recruitment Status : Active, not recruiting
First Posted : January 4, 2013
Results First Posted : September 25, 2018
Last Update Posted : March 30, 2020
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Limited )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatocellular Carcinoma (HCC)
Interventions Drug: Lenvatinib
Drug: Sorafenib
Enrollment 954
Recruitment Details Participants took part in the study at 154 investigative sites in Australia, Belgium, Canada, China, France, Germany, HongKong, Israel, Italy, Japan,SouthKorea, Malaysia,Philippines,Poland,Russia,Singapore,Spain,Taiwan,Thailand,United Kingdom and the United States from 1 March 2013 to 13 November 2016 (date of data cutoff for the primary analysis).
Pre-assignment Details A total of 1,492 participants were screened, 954 participants were enrolled and randomized, out of which 951 participants were treated in the study.
Arm/Group Title Lenvatinib Sorafenib
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 478 476
Treated 476 475
Completed 0 0
Not Completed 478 476
Reason Not Completed
Death             351             350
Lost to Follow-up             5             11
Withdrawal by Subject             13             8
Ongoing as of data-cut off             109             107
Arm/Group Title Lenvatinib Sorafenib Total
Hide Arm/Group Description 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. Participants received sorafenib 400 mg tablets, orally, twice daily in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. Total of all reporting groups
Overall Number of Baseline Participants 478 476 954
Hide Baseline Analysis Population Description
The full analysis set (FAS) included all participants who were randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 478 participants 476 participants 954 participants
61.3  (11.69) 61.2  (12.01) 61.3  (11.84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 478 participants 476 participants 954 participants
Female
73
  15.3%
75
  15.8%
148
  15.5%
Male
405
  84.7%
401
  84.2%
806
  84.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 478 participants 476 participants 954 participants
Hispanic or Latino
6
   1.3%
11
   2.3%
17
   1.8%
Not Hispanic or Latino
472
  98.7%
465
  97.7%
937
  98.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 478 participants 476 participants 954 participants
American Indian or Alaska Native
1
   0.2%
0
   0.0%
1
   0.1%
Asian
334
  69.9%
326
  68.5%
660
  69.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.2%
1
   0.1%
Black or African American
7
   1.5%
6
   1.3%
13
   1.4%
White
135
  28.2%
141
  29.6%
276
  28.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   0.2%
2
   0.4%
3
   0.3%
1.Primary Outcome
Title Overall Survival (OS)
Hide Description 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.
Time Frame From date of randomization until date of death from any cause (approximately up to 3.8 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all participants who were randomized.
Arm/Group Title Lenvatinib Sorafenib
Hide Arm/Group Description:
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.
Participants received sorafenib 400 mg tablets, orally, twice daily in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Overall Number of Participants Analyzed 478 476
Median (95% Confidence Interval)
Unit of Measure: months
13.6
(12.1 to 14.9)
12.3
(10.4 to 13.9)
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all participants who were randomized.
Arm/Group Title Lenvatinib Sorafenib
Hide Arm/Group Description:
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.
Participants received sorafenib 400 mg tablets, orally, twice daily in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Overall Number of Participants Analyzed 478 476
Median (95% Confidence Interval)
Unit of Measure: months
7.4
(6.9 to 8.8)
3.7
(3.6 to 4.6)
3.Secondary Outcome
Title Time to Progression (TTP)
Hide Description 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.
Time Frame The time from the date of randomization to the date of first documentation of disease progression (approximately up to 3.8 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all participants who were randomized.
Arm/Group Title Lenvatinib Sorafenib
Hide Arm/Group Description:
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.
Participants received sorafenib 400 mg tablets, orally, twice daily in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Overall Number of Participants Analyzed 478 476
Median (95% Confidence Interval)
Unit of Measure: months
8.9
(7.4 to 9.2)
3.7
(3.6 to 5.4)
4.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all participants who were randomized.
Arm/Group Title Lenvatinib Sorafenib
Hide Arm/Group Description:
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.
Participants received sorafenib 400 mg tablets, orally, twice daily in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Overall Number of Participants Analyzed 478 476
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
24.1
(20.2 to 27.9)
9.2
(6.6 to 11.8)
5.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Baseline up to Off-Treatment Visit (approximately up to 3.8 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all participants who were randomized.
Arm/Group Title Lenvatinib Sorafenib
Hide Arm/Group Description:
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.
Participants received sorafenib 400 mg tablets, orally, twice daily in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Overall Number of Participants Analyzed 478 476
Median (95% Confidence Interval)
Unit of Measure: months
1.7
(1.05 to 1.84)
1.8
(1.05 to 1.84)
6.Secondary Outcome
Title Time to Clinically Meaningful Worsening of HRQoL Assessed Using - EORTC QLQ- Hepatocellular Carcinoma Domain (HCC 18)
Hide Description 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.
Time Frame Baseline up to Off-Treatment Visit (approximately up to 3.8 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all participants who were randomized.
Arm/Group Title Lenvatinib Sorafenib
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 478 476
Median (95% Confidence Interval)
Unit of Measure: months
Fatigue
1.9
(1.81 to 1.97)
1.8
(1.74 to 1.87)
Jaundice
4.6
(3.72 to 5.52)
3.7
(2.86 to 4.73)
Body Image
2.8
(2.73 to 3.68)
1.9
(1.84 to 2.73)
Nutrition
4.1
(3.68 to 5.52)
2.8
(2.04 to 3.06)
Pain
2.7
(1.97 to 2.83)
2.8
(2.73 to 3.72)
Fever
5.5
(4.57 to 6.51)
3.7
(2.99 to 5.52)
Sex Life
7.4
(5.46 to 9.17)
6.7
(4.60 to 13.78)
Abdominal swelling
7.4
(5.52 to 9.24)
7.4
(5.46 to 10.13)
7.Secondary Outcome
Title Time to Clinically Meaningful Worsening of HRQoL Assessed Using EuroQol Five Dimension Health Questionnaire (EQ-5D-3L)
Hide Description The EuroQol five dimension health questionnaire (EQ-5D-3L) was a health profile questionnaire that assessed 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.
Time Frame Baseline up to Off-Treatment Visit (approximately up to 3.8 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all participants who were randomized.
Arm/Group Title Lenvatinib Sorafenib
Hide Arm/Group Description:
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.
Participants received sorafenib 400 mg tablets, orally, twice daily in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Overall Number of Participants Analyzed 478 476
Median (95% Confidence Interval)
Unit of Measure: months
VAS
2.8
(2.17 to 3.65)
1.9
(1.84 to 2.33)
HUI
2.8
(1.97 to 3.52)
1.9
(1.84 to 2.66)
8.Secondary Outcome
Title Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib
Hide Description AUC was assessed on Cycle 1 Day 1, Cycle 2 Day 2 and Cycle 1 Day 15. Summarized data for all time points was reported.
Time Frame Cycle 1 Day 1, Cycle 1 Day 2: 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Lenvatinib 8 mg Lenvatinib 12 mg
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 150 318
Mean (Standard Deviation)
Unit of Measure: nanogram*hour per milliliter (ng*h/mL)
1969.6  (743.0) 2120.9  (685.6)
9.Other Pre-specified Outcome
Title Disease Control Rate (DCR)
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all participants who were randomized.
Arm/Group Title Lenvatinib Sorafenib
Hide Arm/Group Description:
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.
Participants received sorafenib 400 mg tablets, orally, twice daily in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Overall Number of Participants Analyzed 478 476
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
75.5
(71.7 to 79.4)
60.5
(56.1 to 64.9)
10.Other Pre-specified Outcome
Title Clinical Benefit Rate (CBR)
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all participants who were randomized.
Arm/Group Title Lenvatinib Sorafenib
Hide Arm/Group Description:
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.
Participants received sorafenib 400 mg tablets, orally, twice daily in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Overall Number of Participants Analyzed 478 476
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
59.0
(54.6 to 63.4)
38.4
(34.1 to 42.8)
11.Other Pre-specified Outcome
Title Percent Change From Baseline in Serum Biomarker
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Lenvatinib Sorafenib
Hide Arm/Group Description:
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.
Participants received sorafenib 400 mg tablets, orally, twice daily in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Overall Number of Participants Analyzed 66 48
Median (Standard Deviation)
Unit of Measure: percent change
ANG 2: Cycle 1 Day 15 Number Analyzed 55 participants 29 participants
-28.1  (15.94) 8.9  (23.96)
ANG 2: Cycle 2 Day 1 Number Analyzed 53 participants 28 participants
-28.8  (16.53) -0.9  (24.06)
ANG 2: Cycle 3 Day 1 Number Analyzed 49 participants 27 participants
-32.2  (23.23) 0.5  (26.62)
ANG 2: Cycle 4 Day 1 Number Analyzed 45 participants 22 participants
-35.6  (22.91) -4.5  (20.05)
ANG 2: Cycle 5 Day 1 Number Analyzed 41 participants 12 participants
-38.9  (19.83) 7.0  (23.25)
ANG 2: Cycle 6 Day 1 Number Analyzed 38 participants 13 participants
-36.7  (23.59) -3.6  (24.82)
ANG 2: Cycle 7 Day 1 Number Analyzed 34 participants 13 participants
-41.4  (21.20) 1.0  (32.83)
ANG 2: Cycle 8 Day 1 Number Analyzed 27 participants 10 participants
-40.2  (25.33) -6.7  (31.26)
ANG 2: Cycle 9 Day 1 Number Analyzed 26 participants 10 participants
-39.6  (14.04) -1.1  (29.68)
ANG 2: Off-Treatment Number Analyzed 40 participants 17 participants
11.7  (99.13) 16.8  (27.88)
FGF19: Cycle 1 Day 15 Number Analyzed 57 participants 30 participants
75.0  (155.01) 1.3  (83.65)
FGF19: Cycle 2 Day 1 Number Analyzed 56 participants 30 participants
66.5  (134.26) 36.6  (119.65)
FGF19: Cycle 3 Day 1 Number Analyzed 50 participants 27 participants
86.9  (123.85) 22.8  (70.58)
FGF19: Cycle 4 Day 1 Number Analyzed 46 participants 23 participants
208.1  (602.11) 46.8  (214.14)
FGF19: Cycle 5 Day 1 Number Analyzed 42 participants 13 participants
152.8  (228.37) -1.0  (40.36)
FGF19: Cycle 6 Day 1 Number Analyzed 40 participants 15 participants
119.8  (203.81) 26.9  (67.13)
FGF19: Cycle 7 Day 1 Number Analyzed 34 participants 14 participants
64.4  (101.97) -5.9  (57.39)
FGF19: Cycle 8 Day 1 Number Analyzed 31 participants 12 participants
95.8  (135.31) 53.9  (113.79)
FGF19: Cycle 9 Day 1 Number Analyzed 26 participants 11 participants
159.3  (202.00) 56.6  (109.46)
FGF19: Off-Treatment Number Analyzed 41 participants 18 participants
140.1  (270.73) 9.0  (64.17)
FGF 21: Cycle 1 Day 15 Number Analyzed 56 participants 29 participants
22.0  (75.22) 4.0  (43.14)
FGF 21: Cycle 2 Day 1 Number Analyzed 54 participants 29 participants
15.7  (77.44) 18.6  (57.18)
FGF 21: Cycle 3 Day 1 Number Analyzed 49 participants 28 participants
38.3  (38.3) 49.4  (76.43)
FGF 21: Cycle 4 Day 1 Number Analyzed 46 participants 22 participants
42.9  (145.43) 32.8  (70.63)
FGF 21: Cycle 5 Day 1 Number Analyzed 41 participants 13 participants
41.0  (95.97) 31.1  (43.15)
FGF 21: Cycle 6 Day 1 Number Analyzed 39 participants 14 participants
52.6  (168.22) 23.2  (40.90)
FGF 21: Cycle 7 Day 1 Number Analyzed 33 participants 13 participants
63.4  (128.34) 23.7  (53.84)
FGF 21 : Cycle 8 Day1 Number Analyzed 32 participants 11 participants
38.3  (115.53) 17.0  (68.51)
FGF 21: Cycle 9 Day1 Number Analyzed 28 participants 10 participants
59.1  (108.39) 68.9  (103.55)
FGF 21: Off-Treatment Number Analyzed 38 participants 18 participants
141.4  (340.51) 104.9  (183.28)
FGF 23: Cycle 1 Day15 Number Analyzed 58 participants 32 participants
23.9  (49.01) -16.3  (36.14)
FGF 23: Cycle 2 Day 1 Number Analyzed 57 participants 31 participants
20.9  (56.91) -6.2  (48.18)
FGF 23: Cycle 3 Day 1 Number Analyzed 53 participants 29 participants
25.5  (45.27) 17.3  (75.25)
FGF 23: Cycle 4 Day 1 Number Analyzed 48 participants 23 participants
29.5  (48.38) 14.2  (49.29)
FGF 23: Cycle 5 Day 1 Number Analyzed 43 participants 15 participants
29.6  (63.69) 1.0  (47.28)
FGF 23: Cycle 6 Day 1 Number Analyzed 41 participants 15 participants
26.3  (54.57) -10.6  (46.15)
FGF 23: Cycle 7 Day 1 Number Analyzed 35 participants 14 participants
31.5  (57.44) 0.7  (46.95)
FGF 23: Cycle 8 Day 1 Number Analyzed 33 participants 12 participants
38.1  (67.35) 2.8  (43.84)
FGF 23: Cycle 9 Day 1 Number Analyzed 28 participants 11 participants
23.2  (62.58) 0.5  (38.74)
FGF 23: Off-Treatment Number Analyzed 42 participants 18 participants
17.8  (73.59) 14.2  (47.11)
PIVKA-II: Cycle 1 Day 15 Number Analyzed 50 participants 28 participants
80.0  (171.41) 166.9  (256.04)
PIVKA-II: Cycle 2 Day 1 Number Analyzed 51 participants 28 participants
169.7  (329.33) 243.8  (416.82)
PIVKA-II: Cycle 3 Day 1 Number Analyzed 47 participants 27 participants
252.4  (611.40) 218.7  (281.45)
PIVKA-II: Cycle 4 Day 1 Number Analyzed 44 participants 22 participants
371.7  (812.45) 196.2  (348.80)
PIVKA-II: Cycle 5 Day 1 Number Analyzed 40 participants 11 participants
628.2  (1752.64) 369.5  (766.59)
PIVKA-II: Cycle 6 Day 1 Number Analyzed 35 participants 13 participants
648.7  (2746.41) 415.7  (554.27)
PIVKA-II: Cycle 7 Day 1 Number Analyzed 31 participants 13 participants
184.8  (352.75) 703.6  (1226.58)
PIVKA-II: Cycle 8 Day 1 Number Analyzed 25 participants 10 participants
277.8  (481.53) 724.0  (1257.87)
PIVKA-II: Cycle 9 Day 1 Number Analyzed 26 participants 10 participants
318.8  (577.21) 859.1  (1492.93)
PIVKA-II: Off-Treatment Number Analyzed 37 participants 17 participants
809.3  (1827.42) 272.5  (489.60)
VEGF: Cycle 1 Day 15 Number Analyzed 59 participants 32 participants
157.5  (300.21) 97.4  (118.43)
VEGF: Cycle 2 Day 1 Number Analyzed 58 participants 31 participants
128.9  (333.85) 94.0  (180.80)
VEGF: Cycle 3 Day 1 Number Analyzed 53 participants 29 participants
97.7  (162.39) 66.0  (124.58)
VEGF: Cycle 4 Day 1 Number Analyzed 48 participants 23 participants
113.4  (231.19) 76.1  (111.20)
VEGF: Cycle 5 Day 1 Number Analyzed 43 participants 15 participants
132.4  (249.59) 116.2  (215.57)
VEGF: Cycle 6 Day 1 Number Analyzed 41 participants 15 participants
113.1  (219.36) 130.9  (341.12)
VEGF: Cycle 7 Day 1 Number Analyzed 35 participants 14 participants
133.1  (383.43) 96.9  (173.77)
VEGF: Cycle 8 Day 1 Number Analyzed 33 participants 12 participants
148.7  (349.58) 181.1  (399.67)
VEGF: Cycle 9 Day 1 Number Analyzed 28 participants 11 participants
129.6  (215.05) 135.6  (267.61)
VEGF: Off-Treatment Number Analyzed 42 participants 18 participants
127.1  (266.64) 147.8  (304.31)
Time Frame All treatment-emergent adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 3.8 years)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lenvatinib Sorafenib
Hide Arm/Group Description 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. Participants received sorafenib 400 mg tablets, orally, twice daily in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
All-Cause Mortality
Lenvatinib Sorafenib
Affected / at Risk (%) Affected / at Risk (%)
Total   350/476 (73.53%)      350/475 (73.68%)    
Hide Serious Adverse Events
Lenvatinib Sorafenib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   205/476 (43.07%)      144/475 (30.32%)    
Blood and lymphatic system disorders     
Anaemia  1  1/476 (0.21%)  1 4/475 (0.84%)  4
Bone marrow failure  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Disseminated intravascular coagulation  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Anaemia vitamin B12 deficiency  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Febrile neutropenia  1  0/476 (0.00%)  0 2/475 (0.42%)  2
Cardiac disorders     
Myocardial infarction  1  4/476 (0.84%)  4 1/475 (0.21%)  1
Atrial fibrillation  1  1/476 (0.21%)  1 1/475 (0.21%)  1
Cardiopulmonary failure  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Acute myocardial infarction  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Atrial flutter  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Heart valve stenosis  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Cardiac failure  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Ear and labyrinth disorders     
Hypoacusis  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Vertigo  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Eye disorders     
Cataract  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Gastrointestinal disorders     
Ascites  1  12/476 (2.52%)  14 11/475 (2.32%)  13
Diarrhoea  1  8/476 (1.68%)  8 2/475 (0.42%)  2
Oesophageal varices haemorrhage  1  7/476 (1.47%)  8 5/475 (1.05%)  6
Abdominal pain  1  6/476 (1.26%)  6 10/475 (2.11%)  10
Vomiting  1  6/476 (1.26%)  6 0/475 (0.00%)  0
Upper gastrointestinal haemorrhage  1  5/476 (1.05%)  5 2/475 (0.42%)  3
Duodenal ulcer haemorrhage  1  3/476 (0.63%)  3 1/475 (0.21%)  1
Nausea  1  3/476 (0.63%)  3 0/475 (0.00%)  0
Abdominal pain upper  1  2/476 (0.42%)  8 0/475 (0.00%)  0
Duodenal ulcer  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Gastric ulcer  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Umbilical hernia  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Abdominal distension  1  1/476 (0.21%)  1 2/475 (0.42%)  2
Abdominal pain lower  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Dyspepsia  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Gastric haemorrhage  1  1/476 (0.21%)  1 3/475 (0.63%)  4
Intestinal haemorrhage  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Pancreatitis acute  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Varices oesophageal  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Colitis  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Enterocolitis  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Food poisoning  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Gastric perforation  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Gastric ulcer haemorrhage  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Gastrointestinal haemorrhage  1  0/476 (0.00%)  0 2/475 (0.42%)  2
Haematochezia  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Haemorrhoids  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Lower gastrointestinal haemorrhage  1  0/476 (0.00%)  0 2/475 (0.42%)  3
Peritoneal haemorrhage  1  0/476 (0.00%)  0 1/475 (0.21%)  1
General disorders     
Asthenia  1  7/476 (1.47%)  7 1/475 (0.21%)  1
Pyrexia  1  6/476 (1.26%)  6 5/475 (1.05%)  6
General physical health deterioration  1  5/476 (1.05%)  5 3/475 (0.63%)  3
Oedema peripheral  1  3/476 (0.63%)  3 1/475 (0.21%)  1
Fatigue  1  2/476 (0.42%)  2 2/475 (0.42%)  2
Multiple organ dysfunction syndrome  1  2/476 (0.42%)  2 1/475 (0.21%)  1
Death  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Generalised oedema  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Organ failure  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Peripheral swelling  1  1/476 (0.21%)  1 1/475 (0.21%)  2
Sudden death  1  1/476 (0.21%)  1 2/475 (0.42%)  2
Hepatobiliary disorders     
Hepatic failure  1  14/476 (2.94%)  14 8/475 (1.68%)  8
Jaundice cholestatic  1  7/476 (1.47%)  7 3/475 (0.63%)  3
Portal vein thrombosis  1  4/476 (0.84%)  4 0/475 (0.00%)  0
Cholangitis  1  3/476 (0.63%)  4 2/475 (0.42%)  2
Hepatic cirrhosis  1  3/476 (0.63%)  3 0/475 (0.00%)  0
Bile duct obstruction  1  2/476 (0.42%)  4 0/475 (0.00%)  0
Bile duct stone  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Cholecystitis  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Acute hepatic failure  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Biliary dilatation  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Cholecystitis acute  1  1/476 (0.21%)  1 2/475 (0.42%)  2
Chronic hepatic failure  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Haemobilia  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Hepatic function abnormal  1  1/476 (0.21%)  1 4/475 (0.84%)  4
Hepatic pain  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Hepatorenal syndrome  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Hydrocholecystis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Hyperbilirubinaemia  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Jaundice  1  1/476 (0.21%)  1 4/475 (0.84%)  4
Liver injury  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Infections and infestations     
Sepsis  1  7/476 (1.47%)  7 3/475 (0.63%)  3
Pneumonia  1  5/476 (1.05%)  5 4/475 (0.84%)  4
Cellulitis  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Gastroenteritis  1  2/476 (0.42%)  2 1/475 (0.21%)  1
Liver abscess  1  2/476 (0.42%)  2 1/475 (0.21%)  1
Lung infection  1  2/476 (0.42%)  2 1/475 (0.21%)  1
Peritonitis bacterial  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Urinary tract infection  1  2/476 (0.42%)  3 0/475 (0.00%)  0
Appendiceal abscess  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Bacteraemia  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Biliary tract infection  1  1/476 (0.21%)  1 1/475 (0.21%)  1
Dengue fever  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Diverticulitis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Escherichia sepsis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Gastrointestinal viral infection  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Groin abscess  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Infection  1  1/476 (0.21%)  1 1/475 (0.21%)  1
Infectious pleural effusion  1  1/476 (0.21%)  1 1/475 (0.21%)  1
Lung abscess  1  1/476 (0.21%)  1 1/475 (0.21%)  1
Perihepatic abscess  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Periodontitis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Pleural infection  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Postoperative abscess  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Pulmonary tuberculosis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Salmonellosis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Scrotal infection  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Septic shock  1  1/476 (0.21%)  1 1/475 (0.21%)  1
Tuberculosis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Urinary tract infection enterococcal  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Urosepsis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Acute sinusitis  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Aspergillus infection  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Bronchitis  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Device related infection  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Diabetic foot infection  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Lower respiratory tract infection  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Ophthalmic herpes simplex  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Perineal abscess  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Pneumonia escherichia  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Upper respiratory tract infection  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Injury, poisoning and procedural complications     
Accidental overdose  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Fall  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Intentional overdose  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Spinal compression fracture  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Thoracic vertebral fracture  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Foreign body  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Pneumothorax traumatic  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Spinal fracture  1  0/476 (0.00%)  0 2/475 (0.42%)  2
Subarachnoid haemorrhage  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Traumatic haematoma  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Investigations     
Blood bilirubin increased  1  7/476 (1.47%)  7 1/475 (0.21%)  1
Aspartate aminotransferase increased  1  2/476 (0.42%)  2 1/475 (0.21%)  1
Alanine aminotransferase increased  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Blood pressure decreased  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Clostridium test positive  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Hepatic enzyme increased  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Neutrophil count decreased  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Weight decreased  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Haemoglobin decreased  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Platelet count decreased  1  0/476 (0.00%)  0 2/475 (0.42%)  2
Metabolism and nutrition disorders     
Decreased appetite  1  11/476 (2.31%)  12 2/475 (0.42%)  2
Hyponatraemia  1  3/476 (0.63%)  3 1/475 (0.21%)  1
Dehydration  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Hyperkalaemia  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Cachexia  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Diabetes mellitus  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Hypercalcaemia  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Hypoalbuminaemia  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Hypocalcaemia  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Hypoglycaemia  1  1/476 (0.21%)  1 1/475 (0.21%)  1
Hypomagnesaemia  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Hypoproteinaemia  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  2/476 (0.42%)  2 5/475 (1.05%)  5
Muscular weakness  1  2/476 (0.42%)  2 1/475 (0.21%)  1
Pathological fracture  1  2/476 (0.42%)  2 5/475 (1.05%)  5
Bone pain  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Flank pain  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Intervertebral disc protrusion  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Lumbar spinal stenosis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Neck pain  1  1/476 (0.21%)  1 1/475 (0.21%)  1
Osteoarthritis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Pain in extremity  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Rhabdomyolysis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Spinal column stenosis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Spinal osteoarthritis  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant neoplasm progression  1  10/476 (2.10%)  10 14/475 (2.95%)  14
Cancer pain  1  4/476 (0.84%)  4 0/475 (0.00%)  0
Tumour haemorrhage  1  3/476 (0.63%)  3 3/475 (0.63%)  3
Liver carcinoma ruptured  1  2/476 (0.42%)  2 1/475 (0.21%)  1
Metastases to central nervous system  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Metastases to spine  1  2/476 (0.42%)  2 1/475 (0.21%)  1
Infected neoplasm  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Intracranial tumour haemorrhage  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Meningioma  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Metastases to bone  1  1/476 (0.21%)  1 2/475 (0.42%)  2
Renal cell carcinoma  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Tumour necrosis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Tumour pain  1  1/476 (0.21%)  1 2/475 (0.42%)  2
Tumour rupture  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Lung neoplasm malignant  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Malignant ascites  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Malignant pleural effusion  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Plasma cell myeloma  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Nervous system disorders     
Hepatic encephalopathy  1  21/476 (4.41%)  31 3/475 (0.63%)  4
Cerebral haemorrhage  1  3/476 (0.63%)  3 0/475 (0.00%)  0
Coma hepatic  1  3/476 (0.63%)  3 1/475 (0.21%)  1
Cerebral infarction  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Cerebrovascular accident  1  2/476 (0.42%)  2 1/475 (0.21%)  1
Headache  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Seizure  1  2/476 (0.42%)  2 1/475 (0.21%)  1
Spinal cord compression  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Diplegia  1  1/476 (0.21%)  1 1/475 (0.21%)  1
Disturbance in attention  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Dizziness  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Facial paralysis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Paralysis recurrent laryngeal nerve  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Posterior reversible encephalopathy syndrome  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Syncope  1  1/476 (0.21%)  2 0/475 (0.00%)  0
Transient ischaemic attack  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Basal ganglia haemorrhage  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Encephalopathy  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Ischaemic stroke  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Loss of consciousness  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Thrombotic cerebral infarction  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Psychiatric disorders     
Confusional state  1  1/476 (0.21%)  1 2/475 (0.42%)  2
Major depression  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Suicide attempt  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  3/476 (0.63%)  3 2/475 (0.42%)  2
Proteinuria  1  3/476 (0.63%)  3 0/475 (0.00%)  0
Renal failure  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Renal impairment  1  2/476 (0.42%)  2 2/475 (0.42%)  2
Haematuria  1  1/476 (0.21%)  1 0/475 (0.00%)  0
IgA nephropathy  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Renal tubular necrosis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Reproductive system and breast disorders     
Pelvic pain  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  5/476 (1.05%)  5 2/475 (0.42%)  2
Pulmonary embolism  1  4/476 (0.84%)  4 2/475 (0.42%)  2
Pneumonia aspiration  1  3/476 (0.63%)  3 0/475 (0.00%)  0
Respiratory failure  1  3/476 (0.63%)  3 3/475 (0.63%)  3
Hepatopulmonary syndrome  1  2/476 (0.42%)  2 0/475 (0.00%)  0
Acute respiratory failure  1  1/476 (0.21%)  1 1/475 (0.21%)  1
Hiccups  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Necrotising bronchiolitis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Non-cardiogenic pulmonary oedema  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Oropharyngeal pain  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Pneumothorax  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Pulmonary infarction  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Pleural effusion  1  0/476 (0.00%)  0 2/475 (0.42%)  2
Pneumonitis  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Skin and subcutaneous tissue disorders     
Intertrigo  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Seborrhoeic dermatitis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Drug eruption  1  0/476 (0.00%)  0 2/475 (0.42%)  2
Erythema multiforme  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Palmar-plantar erythrodysaesthesia syndrome  1  0/476 (0.00%)  0 3/475 (0.63%)  3
Psoriasis  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Vascular disorders     
Aortic dissection  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Circulatory collapse  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Deep vein thrombosis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Thrombophlebitis  1  1/476 (0.21%)  1 0/475 (0.00%)  0
Hypotension  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Shock  1  0/476 (0.00%)  0 1/475 (0.21%)  1
Thrombophlebitis superficial  1  0/476 (0.00%)  0 1/475 (0.21%)  1
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lenvatinib Sorafenib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   469/476 (98.53%)      469/475 (98.74%)    
Blood and lymphatic system disorders     
Anaemia  1  34/476 (7.14%)  40 42/475 (8.84%)  46
Thrombocytopenia  1  33/476 (6.93%)  44 28/475 (5.89%)  36
Endocrine disorders     
Hypothyroidism  1  78/476 (16.39%)  79 8/475 (1.68%)  8
Gastrointestinal disorders     
Abdominal distension  1  38/476 (7.98%)  49 24/475 (5.05%)  26
Abdominal pain  1  79/476 (16.60%)  105 83/475 (17.47%)  99
Abdominal pain upper  1  58/476 (12.18%)  66 40/475 (8.42%)  48
Ascites  1  61/476 (12.82%)  68 37/475 (7.79%)  42
Constipation  1  76/476 (15.97%)  89 52/475 (10.95%)  60
Diarrhoea  1  183/476 (38.45%)  325 219/475 (46.11%)  350
Dyspepsia  1  31/476 (6.51%)  40 18/475 (3.79%)  19
Nausea  1  91/476 (19.12%)  111 68/475 (14.32%)  77
Stomatitis  1  45/476 (9.45%)  55 56/475 (11.79%)  67
Vomiting  1  73/476 (15.34%)  102 36/475 (7.58%)  57
General disorders     
Asthenia  1  52/476 (10.92%)  74 48/475 (10.11%)  54
Fatigue  1  140/476 (29.41%)  155 118/475 (24.84%)  129
Oedema peripheral  1  64/476 (13.45%)  83 32/475 (6.74%)  39
Pyrexia  1  63/476 (13.24%)  74 60/475 (12.63%)  68
Investigations     
Alanine aminotransferase increased  1  53/476 (11.13%)  66 52/475 (10.95%)  66
Aspartate aminotransferase increased  1  64/476 (13.45%)  80 80/475 (16.84%)  100
Blood alkaline phosphatase increased  1  32/476 (6.72%)  39 29/475 (6.11%)  32
Blood bilirubin increased  1  66/476 (13.87%)  92 62/475 (13.05%)  74
Electrocardiogram QT prolonged  1  33/476 (6.93%)  45 24/475 (5.05%)  47
Gamma-glutamyltransferase increased  1  37/476 (7.77%)  39 26/475 (5.47%)  27
Neutrophil count decreased  1  40/476 (8.40%)  69 11/475 (2.32%)  14
Platelet count decreased  1  87/476 (18.28%)  117 57/475 (12.00%)  66
Weight decreased  1  147/476 (30.88%)  165 106/475 (22.32%)  113
White blood cell count decreased  1  46/476 (9.66%)  80 23/475 (4.84%)  37
Metabolism and nutrition disorders     
Decreased appetite  1  159/476 (33.40%)  192 125/475 (26.32%)  137
Hypoalbuminaemia  1  43/476 (9.03%)  49 38/475 (8.00%)  42
Musculoskeletal and connective tissue disorders     
Arthralgia  1  42/476 (8.82%)  48 20/475 (4.21%)  25
Back pain  1  48/476 (10.08%)  53 28/475 (5.89%)  29
Musculoskeletal pain  1  47/476 (9.87%)  50 24/475 (5.05%)  25
Pain in extremity  1  37/476 (7.77%)  47 18/475 (3.79%)  21
Nervous system disorders     
Headache  1  45/476 (9.45%)  53 38/475 (8.00%)  40
Psychiatric disorders     
Insomnia  1  33/476 (6.93%)  35 27/475 (5.68%)  29
Renal and urinary disorders     
Proteinuria  1  116/476 (24.37%)  162 54/475 (11.37%)  74
Respiratory, thoracic and mediastinal disorders     
Cough  1  45/476 (9.45%)  54 36/475 (7.58%)  43
Dysphonia  1  113/476 (23.74%)  131 57/475 (12.00%)  66
Epistaxis  1  34/476 (7.14%)  34 15/475 (3.16%)  17
Skin and subcutaneous tissue disorders     
Alopecia  1  14/476 (2.94%)  15 119/475 (25.05%)  123
Palmar-plantar erythrodysaesthesia syndrome  1  128/476 (26.89%)  142 246/475 (51.79%)  286
Pruritus  1  34/476 (7.14%)  37 34/475 (7.16%)  37
Rash  1  46/476 (9.66%)  51 76/475 (16.00%)  87
Vascular disorders     
Hypertension  1  201/476 (42.23%)  253 144/475 (30.32%)  166
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Eisai Medical Services
Organization: Eisai, Inc.
Phone: 1-888-422-4743
EMail: esi_medinfo@eisai.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eisai Inc. ( Eisai Limited )
ClinicalTrials.gov Identifier: NCT01761266    
Other Study ID Numbers: E7080-G000-304
2012-002992-33 ( EudraCT Number )
First Submitted: January 2, 2013
First Posted: January 4, 2013
Results First Submitted: August 27, 2018
Results First Posted: September 25, 2018
Last Update Posted: March 30, 2020