A Study of Dovitinib Versus Sorafenib in Adult Patients With Hepatocellular Carcinoma (HCC) as a First Line Treatment

The overall survival (OS), defined as the time from date of randomization to the date of death from any cause. If a patient was not known to have died at the date of analysis cut-off, OS was censored at the last date of contact. Survival information was collected every 6 wks until at least 130 deaths have been observed

Time frame: Every 6 weeks from date of randomization until the patient has progressed, or the patient can no longer be followed, or at least 130 deaths have been observed in the study, whichever came first.

Population: The Full Analysis Set (FAS) comprises of all patients to whom study treatment had been assigned by randomization. According to the intent to treat principle, patients were analyzed according to the treatment (and strata) they were assigned to during the randomization procedure.

Disease Control Rate (DCR) is defined as the proportion of patients whose best overall response is either complete response \[CR\], partial response \[PR\] or stable disease \[SD\] according to RECIST 1.1.

Time frame: Every 6 weeks from date of randomization until the patient has progressed, or the patient can no longer be followed, or at least 130 deaths have been observed in the study, whichever came first.

Population: The Full Analysis Set (FAS) comprises of all patients to whom study treatment had been assigned by randomization. According to the intent to treat principle, patients were analyzed according to the treatment (and strata) they were assigned to during the randomization procedure.

The mean AUC from time zero to the last measurable concentration sampling time (t last) (mass x time x volume-1)

Time frame: Week 1 day 1, week 4 day 5

Population: The Full-PK analysis set: all patients who were selected for full PK sampling and provided at least one evaluable PK concentration profile

Cmax will be evaluated after a single dose of TKI258 following a 5 days on/2 days off dosing schedule. Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after a single dose administration (mass x volume - 1).

Time frame: Week 1 day 1, week 4 day 5

Population: The Full-PK analysis set: all patients who were selected for full PK sampling and provided at least one evaluable PK concentration profile

Tmax will be evaluated after a single dose of TKI258 following a 5 days on/2 days off dosing schedule. Tmax is the time to to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after a single dose administration (time)

Time frame: Week 1 day 1, week 4 day 5

Population: The Full-PK analysis set: all patients who were selected for full PK sampling and provided at least one evaluable PK concentration profile

Time to definitive deterioration on ECOG PS scale (by at least one point) was defined as the time from the date of randomization to the date of definitive deterioration of the ECOG PS by at least one category of the score from baseline or to the date of death whichever occurred earlier. 0 is Fully active, able to carry on all pre-disease performance without restriction, 1 is Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light housework, office work and 2 is ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.

Time frame: Every 6 weeks from date of randomization until the patient has progressed, or the patient can no longer be followed, or at least 130 deaths have been observed in the study, whichever came first

Population: The Full Analysis Set (FAS): all patients to whom study treatment had been assigned by randomization. According to the intent to treat principle, patients were analyzed according to the treatment (and strata) they were assigned to during the randomization procedure. Only Total number of definitive deterioration events included in the analysis

Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). For target lesions, disease progression mean at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression refers to unequivocal progression of existing non-target lesions. In addition, the appearance of new lesions is always considered as disease progression.

Time frame: Every 6 weeks from date of randomization until the patient has progressed, or the patient can no longer be followed, or at least 130 deaths have been observed in the study, whichever came first.

Population: The Full Analysis Set (FAS) comprises of all patients to whom study treatment had been assigned by randomization. According to the intent to treat principle, patients were analyzed according to the treatment (and strata) they were assigned to during the randomization procedure.