Nexavar® Versus Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer

PFS=time from randomization to first observed disease progression (radiological according to central assessment or clinical due to bone irradiation, whichever is earlier), or death due to any cause, if death occurred before progression. Progression was assessed by RECIST criteria, version 1.0, modified for bone lesions. PFS for participants without disease progression or death at the time of analysis or unblinding were censored at the last date of tumor assessment before unblinding. Participants with no tumor evaluation after baseline were censored at Day 1. PD (Progression Disease)=At least a 20% increase in sum of longest diameters (LD) of measured lesions taking as reference the smallest sum LD on study since the treatment started or the appearance of 1 or more new lesions. New lesions also constituted PD. In exceptional circumstances, unequivocal progression of a nonmeasured lesion may have been accepted as evidence of disease progression in participants with measurable disease.

Time frame: Final analysis to be performed when approximately 267 progression-free survival events (centrally assessed) had occurred, study duration approximately three years

Population: Full Analysis Set (FAS). The primary population for efficacy analysis was the FAS. The FAS was identical to the intent-to-treat (ITT) population, which was defined as all randomized participants. Participants were analyzed as randomized.

Sorafenib AUC(0-12h),ss (area under the concentration time curve from time 0 to 12 hours at steady state) was estimated from the steady state plasma concentration.

Time frame: A single pharmacokinetic plasma sample was collected at steady state (after 14 days of uninterrupted, unmodified sorafenib dosing)

Population: Pharmacokinetic (PK) analysis set=participants with PK data collected after 14 days of uninterrupted and unmodified dosing of sorafenib. If an interruption occurred within 14 days prior to the sample, no doses may be missed for 3 days prior to the sample, and no more than 3 doses could be missed 4 to 14 days prior to the sample collection date.

Disease control rate was defined as the proportion of subjects whose best response was complete response (CR), partial response (PR), or stable disease (SD). Per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, CR and PR were to be confirmed by another scan at least 4 weeks later; SD had to be documented at least 4 weeks after date of randomization. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum. SD = steady state of disease which is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Time frame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

Population: Per protocol set (PPS). A participant was included in the PPS if he/she was randomized and was evaluable for tumor response based on imaging data, had exposure to study medication, and had no major protocol deviations.

Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum.

Time frame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

Population: FAS - responders only

The magnitude of change from baseline in target lesion size in evaluable participants with scans was determined.

Time frame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

Population: PPS

Overall survival was defined as the time (days) from date of randomization to date of death due to any cause. Subjects still alive at the time of analysis were censored at their date of last contact. Since the median value could not be estimated due to censored data, the percentage of participants who died is presented.

Time frame: From randomization of the first subject until the database cut-off (30 AUG 2017), study duration approximately eight years

Population: Full Analysis Set (FAS)

Response rate was defined as the proportion of subjects whose best response was CR or PR. Per RECIST, CR and PR was to be confirmed by another scan at least 4 weeks later. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum.

Time frame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

Population: PPS

Time to progression was defined at the time (days) from randomization to progression (based on central assessment \[radiological and clinical progression due to bone irradiation\])

Time frame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

Population: FAS