Study of Lenvatinib (E7080) in Participants With Advanced Hepatocellular Carcinoma (HCC)

The MTD was defined as the highest dose level at which no more than 1 of 6 participants had a dose limiting toxicities (DLT). DLT was defined as any of the following events: grade 4 or higher hematologic toxicity or grade 3 thrombocytopenia that required blood transfusion, grade 3 or higher nonhematologic toxicity, grade 4 hypertension uncontrolled by antihypertensive drug(s), aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than (\>) 10.0\*upper limit of normal (ULN), proteinuria 4+ by urine dipstick, proteinuria 3+ by urine dipstick was to be monitored by 24-hour urine collection, proteinuria \>3.5 gram (g) for 24 hours, diarrhea/vomiting/nausea of grade 3 or higher that was uncontrollable despite maximal supportive therapies and abnormal clinical laboratory values that required no treatment, grade 3 proteinuria by dipstick, diarrhea/vomiting/nausea that was managed with supportive therapies were not considered as DLT.

Time frame: Up to 28 days (Cycle1)

Population: Safety analysis set (SAS) included all participants who received at least 1 dose of lenvatinib, and had at least 1 post baseline safety evaluation.

TTP was defined as the time from the date of registration to the date when progressive disease (PD) was first confirmed. PD was evaluated according to modified response evaluation criteria in solid tumors (mRECIST) by an independent imaging review. PD was defined as at least a 20 percent (%) increase in the sum of long diameter (LD) of target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 millimeter (mm) (including new lesions).

Time frame: From day of registration to the day when PD was first confirmed (approximately up to 6.1 years)

Population: Per protocol set (PPS) included all participants in full analysis set (FAS), who showed greater than or equal to (\>=) 75% cumulative treatment compliance, had a baseline and post baseline tumor response assessment, and completed at least 2 cycles or discontinued during the 2 cycles due to PD or death.

BOR was performed using RECIST1.1 and was measured as complete response (CR) defined as when an overall response of CR was obtained 2 or more consecutive times at intervals of at least 28 days (the date when the second overall response of CR was confirmed and the BOR established as CR was regarded as the CR confirmed date), partial response (PR) defined as when the overall response of PR or better (CR or PR) was obtained 2 or more consecutive times at intervals of at least 28 days (the date when the second overall response of PR was confirmed and the BOR established as PR will be regarded as the PR confirmed date), PD defined as when the BOR was neither CR, PR, or stable disease (SD), and the overall response was PD, SD defined as when the BOR obtained was neither CR nor PR, but no PD from the initial administration to the end of Cycle 2 and the overall response of SD or better occurred at least once and not evaluable (NE) was when the overall response was NE in all cases.

Time frame: Every 8 weeks (approximately up to 18.4 months)

Population: Efficacy analysis set (EAS) included all participants who received at least 1 dose of lenvatinib, and had at least 1 postbaseline efficacy evaluation.

DCR was measured by RECIST 1.1 and defined as CR which was defined as disappearance of all target lesions (a short diameter was \<10 mm if it exists in a lymph node) plus PR which was defined as at least 30% decrease in the sum of the long diameter (hereafter referred to as sum of LD) of all target lesions, as compared with baseline summed LD plus SD which was reduction in tumor volume of less than 50% or an increase in the volume of 1 or more measurable lesions of less than 25% without the appearance of any new lesions which was neither tumor shrinkage corresponding to PR nor tumor expansion corresponding to PD.

Time frame: Up to Week 16

Population: EAS included participants who received at least 1 dose of lenvatinib, and had at least 1 postbaseline efficacy evaluation.

ORR was defined as the percentage of participants who achieved a tumor response measured by RECIST 1.1 of CR defined as disappearance of all target lesions (a short diameter is less than (\<)10 mm if it exists in a lymph node) plus PR defined as at least 30% decrease in the sum of the long diameter LD (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.

Time frame: From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)

Population: EAS included participants who received at least 1 dose of lenvatinib, and had at least 1 postbaseline efficacy evaluation.

DCR was measured by mRECIST and defined as CR which was defined as disappearance of all target lesions (a short diameter is \<10 mm if it exists in a lymph node) plus PR which was defined as at least 30% decrease in the sum of the long diameter (hereafter referred to as sum of LD) of all target lesions, as compared with baseline summed LD plus SD which was reduction in tumor volume of less than 50% or an increase in the volume of 1 or more measurable lesions of less than 25% without the appearance of any new lesions which was neither tumor shrinkage corresponding to PR nor tumor expansion corresponding to PD.

Time frame: Weeks 8 and 16

Population: PPS included all participants in the FAS showed \>=75% cumulative treatment compliance, had a baseline and post baseline tumor response assessment, and completed at least 2 cycles or discontinued during the 2 cycles due to PD or death.

ORR was defined as the percentage of participants who achieved a tumor response measured by mRECIST of CR defined as disappearance of all target lesions (a short diameter is \<10 mm if it exists in a lymph node) plus PR defined as at least 30% decrease in the sum of the long diameter LD (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.

Time frame: From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)

Population: PPS included all participants in the FAS who showed \>=75% cumulative treatment compliance, had a baseline and post baseline tumor response assessment, and completed at least 2 cycles or discontinued during the 2 cycles due to PD or death.

OS was defined as the time from the date of registration until the date of death.

Time frame: From day of registration to the day of death (approximately 6.1 years)

Population: PPS included all participants in the FAS who showed \>=75% cumulative treatment compliance, had a baseline and post baseline tumor response assessment, and completed at least 2 cycles or discontinued during the 2 cycles due to PD or death.

PFS was defined as the time from the date of registration until the date when PD was first confirmed or death (whichever occurred first) as determined by mRECIST and PD was defined as at least a 20% increase in the sum of long diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.

Time frame: From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)

Population: PPS included all participants in the FAS who showed \>=75% cumulative treatment compliance, had a baseline and post baseline tumor response assessment, and completed at least 2 cycles or discontinued during the 2 cycles due to PD or death.