A Study of Vemurafenib (RO5185426) in Participants With Metastatic or Unresectable Papillary Thyroid Cancer Positive for the BRAF V600 Mutation

Best overall response rate was assessed by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Best overall response rate: the percentage of participants with best objective response of complete response (CR) or partial response (PR) (calculated as the number of participants with best response CR or PR divided by the total number of efficacy-evaluable participants). CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \< 10 millimeters (mm). PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters.

Time frame: Up to approximately 4 years

Population: Efficacy population (TKI Naive group only), defined as all enrolled participants who received at least one dose of study treatment and excluding 3 participants in the TKI Experienced group who had previous BRAFi or MEKi treatment or withdrew consent.

Best overall response rate was assessed by the investigators according to RECIST v1.1. Best overall response rate: the percentage of participants with best objective response of CR or PR (calculated as the number of participants with best response CR or PR divided by the total number of efficacy-evaluable participants). CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \< 10 mm. PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters.

Time frame: Up to approximately 4 years

Population: Efficacy population (TKI Experienced group only), defined as all enrolled participants who received at least one dose of study treatment and excluding 3 participants in the TKI Experienced group who had previous BRAFi or MEKi treatment or withdrew consent.

Clinical benefit rate: the percentage of participants with confirmed CR, PR, or stable disease (SD; maintained for at least 6 months) as assessed by investigators according to RECIST v1.1. CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \< 10 mm. PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, compared to the baseline sum diameters.

Time frame: Up to approximately 4 years

Population: Efficacy population, defined as all enrolled participants who received at least one dose of study treatment and excluding 3 participants in the TKI Experienced group who had previous BRAFi or MEKi treatment or withdrew consent.

Duration of response (for participants with confirmed best response CR or PR): the interval between earliest qualifying response and date of progression of disease (PD) or death for any cause, whichever occurred first; participants with no documented progression after CR or PR were censored at the date of last known CR or PR, respectively. CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \< 10 mm. PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters. PD: ≥ 20% increase in the sum of diameters of target lesions, compared to the smallest sum on study.

Time frame: From the date of first qualifying response to the date of PD or death for any cause (up to approximately 4 years)

Population: Efficacy population, defined as all enrolled participants who received at least one dose of study treatment and excluding 3 participants in the TKI Experienced group who had previous BRAFi or MEKi treatment or withdrew consent.

Overall survival: the interval between the date of first treatment to the date of death, regardless of the cause of death; participants who were alive at the time of the analysis were censored at the date of the last known alive; participants with no post baseline information were censored at the time of enrollment.

Time frame: From the date of first treatment to the date of death for any cause (up to approximately 4 years)

Population: Intent-to-Treat population, defined as all enrolled participants.

An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Time frame: Baseline until 28 days after the last dose of study treatment or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 4 years)

Population: Safety population, defined as enrolled participants who received at least one dose of study treatment.

AUC is a measure of the drug or biologic concentration in the body following administration.

Time frame: Up to approximately 4 years

Population: Data were not collected for this outcome.

Progression-free survival: the interval between the day of first treatment and the first documentation of PD or death; participants who were withdrawn from the study without documented progression were censored at the date of the last tumor assessment when the participant was known to be progression-free; participants without post baseline tumor assessments were censored at the time of enrollment. PD: ≥ 20% increase in the sum of diameters of target lesions, compared to the smallest sum on study.

Time frame: From the day of first treatment until the first documented PD or death (up to approximately 4 years)

Population: Efficacy population, defined as all enrolled participants who received at least one dose of study treatment and excluding 3 participants in the TKI Experienced group who had previous BRAFi or MEKi treatment or withdrew consent.