Trial Outcomes & Findings for Study of Lenvatinib in Subjects With Advanced Endometrial Cancer and Disease Progression (NCT NCT01111461)

NCT ID: NCT01111461

Last Updated: 2023-06-22

Results Overview

ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for target lesions assessed by magnetic resonance imaging/computed tomography (MRI/CT) scans, as determined by independent radiologic review. BOR of CR was confirmed by a subsequent CR assessment at least 4 weeks later. BOR of PR was confirmed by a subsequent CR or PR assessment at least 4 weeks later. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to \<10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters. The null hypothesis ORR was ≤10% was tested using 1-sided exact test of a single proportion, at 1-sided 0.05 level. ORR was presented with corresponding 2-sided, 95% confidence interval (CI). ORR=CR+PR

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 133 participants
• Primary outcome timeframe: From the date of first administration of study treatment until all participants completed a minimum of 6 cycles (28-day cycles) or discontinued treatment prior to the end of Cycle 6 (as of 21 May 2012 data cut-off)
• Results posted on: 2023-06-22

Participant Flow

A total of 167 participants were screened for entry into the study. Of these 167 participants, 133 participants met inclusion/exclusion criteria and were treated with at least 1 dose of lenvatinib 24 mg.

Participant milestones

Measure	Lenvatinib 24 mg Lenvatinib hard capsules, 24 mg (two 10-mg capsules and one 4-mg capsule) were self-administered orally once a day in the morning (without regard to food intake) in 28-day cycles. Dose reduction or interruption was allowed for participants who experienced lenvatinib-related toxicity.
Overall Study STARTED	133
Overall Study COMPLETED	82
Overall Study NOT COMPLETED	51

Reasons for withdrawal

Measure	Lenvatinib 24 mg Lenvatinib hard capsules, 24 mg (two 10-mg capsules and one 4-mg capsule) were self-administered orally once a day in the morning (without regard to food intake) in 28-day cycles. Dose reduction or interruption was allowed for participants who experienced lenvatinib-related toxicity.
Overall Study Adverse Event	32
Overall Study Participant choice	11
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	1
Overall Study Other	6

Baseline Characteristics

Study of Lenvatinib in Subjects With Advanced Endometrial Cancer and Disease Progression

Baseline characteristics by cohort

Measure	Lenvatinib 24 mg n=133 Participants Lenvatinib 24 mg was administered orally, once daily continuously in 28-day cycles
Age, Continuous	62.7 years STANDARD_DEVIATION 8.75 • n=5 Participants
Sex: Female, Male Female	133 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Prior Platinum-based Chemotherapy Regimen Carboplatin	80 Participants n=5 Participants
Prior Platinum-based Chemotherapy Regimen Cisplatin	47 Participants n=5 Participants
Prior Platinum-based Chemotherapy Regimen Cisplatin w/Doxorubicin	4 Participants n=5 Participants
Prior Platinum-based Chemotherapy Regimen Taxol [Paclitaxel] w/Carboplatin	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of first administration of study treatment until all participants completed a minimum of 6 cycles (28-day cycles) or discontinued treatment prior to the end of Cycle 6 (as of 21 May 2012 data cut-off)

Population: Full Analysis Set (Intent-to-Treat \[ITT\] Analysis Set) was used and included all participants who received at least 1 dose lenvatinib.

ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for target lesions assessed by magnetic resonance imaging/computed tomography (MRI/CT) scans, as determined by independent radiologic review. BOR of CR was confirmed by a subsequent CR assessment at least 4 weeks later. BOR of PR was confirmed by a subsequent CR or PR assessment at least 4 weeks later. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters. The null hypothesis ORR was ≤10% was tested using 1-sided exact test of a single proportion, at 1-sided 0.05 level. ORR was presented with corresponding 2-sided, 95% confidence interval (CI). ORR=CR+PR

Outcome measures

Measure	Lenvatinib 24 mg n=133 Participants Lenvatinib 24 mg was administered orally, once daily continuously in 28-day cycles
Objective Response Rate (ORR)	14.3 Percentage of participants Interval 8.8 to 21.4

SECONDARY outcome

Timeframe: From date of first administration of study treatment until the date of first documentation of disease progression or date of death, if death occurred prior to disease progression or up to approximately 26 months (as of 21 May 2012 data cut-off)

Population: Full Analysis Set (ITT Population) included all participants who received at least 1 dose of lenvatinib.

PFS was measured as the time from the date of first administration of study treatment until the date of first documentation of disease progression or date of death (whichever occurred first), as determined by independent radiologic review (IRR) and Investigator based on RECIST 1.1. Disease progression per RECIST v1.1 was defined as at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.

Outcome measures

Measure	Lenvatinib 24 mg n=133 Participants Lenvatinib 24 mg was administered orally, once daily continuously in 28-day cycles
Progression Free Survival (PFS) Determined by IRR	5.6 Months Interval 3.7 to 6.3
Progression Free Survival (PFS) Determined by Investigator	5.4 Months Interval 3.7 to 6.7

SECONDARY outcome

Timeframe: From date of first administration of study treatment until the date of death, or up to approximately 32 months (as of 26 Nov 2012 data cut-off)

Population: Full Analysis Set (ITT Population) included all participants who received at least 1 dose of lenvatinib.

OS was the length time in months from the date of first treatment until the date of death from any cause. If death was not observed, OS was censored at the last known alive date or data cut-off. Additional survival follow-up data was collected for all participants who had not withdrawn consent and were alive at the time of the initial survival follow-up as of 26 Nov 2012 data cut-off. Participants who were lost to follow-up at the time of the initial assessment may have been contacted again at the investigator's discretion. Updated survival (based on 26 Nov 2012 cut-off) was derived for these participants if the contact was made successfully.

Outcome measures

Measure	Lenvatinib 24 mg n=133 Participants Lenvatinib 24 mg was administered orally, once daily continuously in 28-day cycles
Overall Survival (OS)	10.6 Months Interval 8.9 to 14.9

SECONDARY outcome

Timeframe: From date of first administration of study treatment until the date of first documentation of disease progression or date of death, if death occurred prior to disease progression, or up to approximately 26 months (as of 21 May 2012 data cut-off)

Population: Full Analysis Set (ITT Population) included all participants who received at least 1 dose of lenvatinib.

DCR was defined as the percentage of participants with BOR of CR or PR or stable disease (SD) based on RECIST 1.1 and SD lasting greater than or equal to 7 weeks, as determined by IRR and Investigator.

Outcome measures

Measure	Lenvatinib 24 mg n=133 Participants Lenvatinib 24 mg was administered orally, once daily continuously in 28-day cycles
Disease Control Rate (DCR) Determined by IRR	60.9 Percentage of participants Interval 52.1 to 69.2
Disease Control Rate (DCR) Determined by Investigator	66.2 Percentage of participants Interval 57.5 to 74.1

SECONDARY outcome

Timeframe: From date of first administration of study treatment until the date of first documentation of disease progression or date of death, if death occurred prior to disease progression, or up to approximately 26 months (as of 21 May 2012 data cut-off)

Population: Full Analysis Set (ITT Population) included all participants who received at least 1 dose of lenvatinib.

CBR was defined as the percentage of participants with BOR of CR or PR or durable stable disease (dSD) [CR + PR + dSD] based on RECIST 1.1. The dSD rate was defined as the percentage of participants with dSD (based on RECIST 1.1 and defined as SD lasting greater than or equal to 23 weeks), as determined by the IRR and Investigator.

Outcome measures

Measure	Lenvatinib 24 mg n=133 Participants Lenvatinib 24 mg was administered orally, once daily continuously in 28-day cycles
Clinical Benefit Rate (CBR) Determined by IRR	37.6 Percentage of participants Interval 29.3 to 46.4
Clinical Benefit Rate (CBR) Determined by Investigator	44.4 Percentage of participants Interval 35.8 to 53.2

SECONDARY outcome

Timeframe: From the administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months.

Population: Safety Analysis Set included all participants who received at least 1 dose of lenvatinib and had at least 1 postbaseline safety evaluation. This was the analysis set for all safety evaluations.

Safety was assessed by monitoring and recording all AEs and SAEs, regular monitoring of hematology, clinical chemistry, and urine values, regular measurement of vital signs, electrocardiograms (ECGs), and echocardiograms.

Outcome measures

Measure	Lenvatinib 24 mg n=133 Participants Lenvatinib 24 mg was administered orally, once daily continuously in 28-day cycles
Number of Participants With Adverse Events (AEs) /Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib Tolerability of Lenvatinib AEs	126 Participants
Number of Participants With Adverse Events (AEs) /Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib Tolerability of Lenvatinib SAEs	62 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Predose and 2 hours postdose on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 2 Day 1

Population: PK analysis set was used and included all participants with an evaluable plasma concentration.

A total of 6 blood samples for pharmacokinetic (PK) analysis were collected from each participant who received lenvatinib once daily.

Outcome measures

Measure	Lenvatinib 24 mg n=133 Participants Lenvatinib 24 mg was administered orally, once daily continuously in 28-day cycles
Summary of Plasma Concentration of Lenvatinib Cycle 1, Day 1 (Pre-dose) n=132	0 ng/mL Standard Deviation 0
Summary of Plasma Concentration of Lenvatinib Cycle 1, Day 1 (2-hour Post-dose) n=132	318.9 ng/mL Standard Deviation 242.16
Summary of Plasma Concentration of Lenvatinib Cycle 1, Day 8 (Pre-dose) n=122	105.6 ng/mL Standard Deviation 121.66
Summary of Plasma Concentration of Lenvatinib Cycle 1, Day 8 (2-hour Post-dose) n=123	352.6 ng/mL Standard Deviation 243.88
Summary of Plasma Concentration of Lenvatinib Cycle 2, Day 1 (Pre-dose) n=107	88.63 ng/mL Standard Deviation 78.768
Summary of Plasma Concentration of Lenvatinib Cycle 2, Day 1 (2-hour Post-dose) n=102	336.8 ng/mL Standard Deviation 222.56

OTHER_PRE_SPECIFIED outcome

Timeframe: Cycle 1 Day 5

Population: Imaging biomarker analysis set included those participants who received at least 1 dose of lenvatinib and had, at minimum, a baseline and 1 postbaseline evaluable imaging assessment. n = 4 participants with evaluable data.

The antiangiogenic and direct antitumor effects of lenvatinib were assessed by analyses of 2 dynamic contrast-enhanced magnetic resonance imaging/diffusion-weighted magnetic resonance imaging (DCE-MRI/DWI MRI) scans obtained on evaluable participants at Baseline and Cycle 1 Day 5. The scans were obtained using standardized acquisition across sites. DWI sequences totaling approximately 30 seconds were acquired during the DCE-MRI scans. Centralized analysis metrics for DCE-MRI included percentage change in initial area under the gadolinium contrast agent time-concentration curve (first 90 seconds, blood normalized) from baseline.

Outcome measures

Measure	Lenvatinib 24 mg n=4 Participants Lenvatinib 24 mg was administered orally, once daily continuously in 28-day cycles
Percentage Change From Baseline for the Imaging Biomarker Parameter of the Area Under the Plasma Concentration Curve Blood Normalized (90) (AUCBN (90)) Median for Total Volume	-34.0 Percentage change Standard Deviation 18.98

OTHER_PRE_SPECIFIED outcome

Timeframe: Cycle 1 Day 5

Population: Imaging biomarker analysis set included those participants who received at least 1 dose of lenvatinib and had, at a minimum, a baseline and 1 postbaseline evaluable imaging assessment. n = 4 participants with evaluable data.

The antiangiogenic and direct antitumor effects of lenvatinib were assessed by analyses of two DCE-MRI/DWI MRI scans obtained on evaluable participants at Baseline and Cycle 1 Day 5. The scans were obtained using standardized acquisition across sites. DWI sequences totaling approximately 30 seconds were acquired during the DCE-MRI scans. Centralized analysis metrics for DCE-MRI included the percentage change in Ktrans for gadolinium chelate movement from the vasculature into the tissue extracellular space from baseline.

Outcome measures

Measure	Lenvatinib 24 mg n=4 Participants Lenvatinib 24 mg was administered orally, once daily continuously in 28-day cycles
Percentage Change From Baseline in the Contrast Volume Transfer Coefficient (Ktrans) Median	-41.5 Percentage change Standard Deviation 22.02

OTHER_PRE_SPECIFIED outcome

Timeframe: Cycle 1 Day 5

Population: Imaging biomarker analysis set included those participants who received at least 1 dose of lenvatinib and had, at a minimum, a baseline and 1 postbaseline evaluable imaging assessment. n = 2 participants with evaluable data.

The antiangiogenic and direct antitumor effects of lenvatinib were assessed by analyses of two DCE-MRI/DWI MRI scans obtained on evaluable participants at Baseline and Cycle 1 Day 5. The scans were obtained using standardized acquisition across sites. DWI sequences totaling approximately 30 seconds were acquired during the DCE-MRI scans. Centralized analysis metrics for DCE-MRI included the percentage change in ADC for gadolinium chelate movement from the vasculature into the tissue extracellular space from baseline.

Outcome measures

Measure	Lenvatinib 24 mg n=2 Participants Lenvatinib 24 mg was administered orally, once daily continuously in 28-day cycles
Percentage Change From Baseline in the Apparent Diffusion Coefficient (ADC) Median	2.1 Percentage change Standard Deviation 2.27

Adverse Events

Lenvatinib 24 mg

Serious events: 62 serious events

Other events: 125 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lenvatinib 24 mg n=133 participants at risk Lenvatinib 24 mg was administered orally, once daily continuously in 28-day cycles
Gastrointestinal disorders Abdominal pain	5.3% 7/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Vomiting	3.8% 5/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Diarrhoea	3.0% 4/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Nausea	2.3% 3/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Colitis	1.5% 2/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Constipation	1.5% 2/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Intestinal obstruction	1.5% 2/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Small intestinal obstruction	1.5% 2/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Abdominal pain upper	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Gastrointestinal fistula	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Ileitis	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Ileus	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Intestinal perforation	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Rectal haemorrhage	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Rectal perforation	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders Asthenia	4.5% 6/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders General physical health deterioration	2.3% 3/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders Device leakage	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders Impaired healing	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders Multi-organ failure	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders Pyrexia	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Vascular disorders Hypertension	4.5% 6/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Vascular disorders Hypotension	3.0% 4/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Vascular disorders Deep vein thrombosis	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Vascular disorders Haematoma	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Metabolism and nutrition disorders Dehydration	4.5% 6/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Metabolism and nutrition disorders Hypocalcaemia	1.5% 2/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Metabolism and nutrition disorders Hypokalaemia	1.5% 2/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Metabolism and nutrition disorders Decreased appetite	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Metabolism and nutrition disorders Metabolic disorder	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Metabolism and nutrition disorders Tumour lysis syndrome	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Renal and urinary disorders Renal failure acute	4.5% 6/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Renal and urinary disorders Azotaemia	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Renal and urinary disorders Proteinuria	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Renal and urinary disorders Renal disorder	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Renal and urinary disorders Renal failure	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.8% 5/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.5% 2/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.5% 2/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Tachypnoea	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Infections and infestations Urinary tract infection	1.5% 2/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Infections and infestations Gastroenteritis	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Infections and infestations Peridiverticular abscess	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Infections and infestations Proctitis infectious	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Infections and infestations Sepsis	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Infections and infestations Urosepsis	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Infections and infestations Wound infection	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Cardiac disorders Angina pectoris	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Cardiac disorders Atrial fibrillation	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Cardiac disorders Bradycardia	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Cardiac disorders Cardiac failure	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Cardiac disorders Cardiac failure congestive	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Cardiac disorders Cardiopulmonary failure	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Cardiac disorders Tachycardia	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Hepatobiliary disorders Cholecystitis	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Hepatobiliary disorders Cholecystitis chronic	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Hepatobiliary disorders Hepatic failure	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour necrosis	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Nervous system disorders Cerebrovascular accident	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Nervous system disorders Headache	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Nervous system disorders Syncope	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Nervous system disorders Transient ischaemic attack	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Psychiatric disorders Mental status changes	1.5% 2/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Psychiatric disorders Confusional state	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Investigations Ejection fraction decreased	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Reproductive system and breast disorders Female genital tract fistula	1.5% 2/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Reproductive system and breast disorders Vaginal haemorrhage	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Injury, poisoning and procedural complications Rib fracture	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Ear and labyrinth disorders Deafness	0.75% 1/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Other adverse events

Measure	Lenvatinib 24 mg n=133 participants at risk Lenvatinib 24 mg was administered orally, once daily continuously in 28-day cycles
Blood and lymphatic system disorders Anaemia	10.5% 14/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Blood and lymphatic system disorders Thrombocytopenia	8.3% 11/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Endocrine disorders Hypothyroidism	17.3% 23/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Eye disorders Vision blurred	5.3% 7/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Abdominal distension	6.8% 9/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Abdominal pain	24.8% 33/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Abdominal pain upper	12.8% 17/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Constipation	18.8% 25/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Diarrhoea	34.6% 46/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Dry mouth	11.3% 15/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Dyspepsia	5.3% 7/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Flatulence	5.3% 7/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Nausea	30.8% 41/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Stomatitis	22.6% 30/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Vomiting	24.1% 32/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders Asthenia	22.6% 30/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders Fatigue	41.4% 55/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders Oedema peripheral	15.0% 20/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Infections and infestations Urinary tract infection	12.8% 17/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Investigations Blood thyroid stimulating hormone increased	6.0% 8/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Investigations Weight decreased	20.3% 27/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Metabolism and nutrition disorders Decreased appetite	33.8% 45/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Metabolism and nutrition disorders Dehydration	6.0% 8/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Metabolism and nutrition disorders Hypokalaemia	12.8% 17/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Metabolism and nutrition disorders Hypomagnesaemia	8.3% 11/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Musculoskeletal and connective tissue disorders Arthralgia	6.8% 9/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Musculoskeletal and connective tissue disorders Back pain	12.0% 16/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Musculoskeletal and connective tissue disorders Pain in extremity	6.0% 8/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Nervous system disorders Dizziness	15.0% 20/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Nervous system disorders Dysgeusia	12.0% 16/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Nervous system disorders Headache	26.3% 35/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Psychiatric disorders Insomnia	5.3% 7/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Renal and urinary disorders Dysuria	6.8% 9/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Renal and urinary disorders Proteinuria	21.1% 28/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Reproductive system and breast disorders Vaginal haemorrhage	6.0% 8/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Cough	14.3% 19/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Dysphonia	20.3% 27/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.8% 17/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Epistaxis	9.8% 13/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Skin and subcutaneous tissue disorders Alopecia	5.3% 7/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	7.5% 10/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Skin and subcutaneous tissue disorders Rash	6.8% 9/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Vascular disorders Hypertension	53.4% 71/133 • From date of administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months. Treatment-emergent adverse events (TEAEs) and serious TEAEs were collected and reported. Safety analysis set included all participants who received at least one dose of study drug. AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Additional Information

Eisai Medical Services

Eisai, Inc.

Phone: 18884224743

Email: esi_medinfo@eisai.com

Results disclosure agreements

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

Restriction type: OTHER