Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma

Overall Survival (OS) was defined as the interval of time between the date of randomization and the date of death due to any cause. For patients who did not die, OS was censored at the date of last contact.

Time frame: From the date of randomization until date of death due to any cause (up to approximately 6 years)

Population: Intent-to-Treat (ITT) Population.

Duration of Response (DOR) was defined as the time from the first documented evidence of a CR (disappearance of all evidence of target lesions) or a PR (at least a 30% reduction from Baseline in the sum of the longest diameter of all target lesions) until disease progression or death due to any cause. PD was defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of at least1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation. Data were summarized per RECIST, Version 1.1.

Time frame: From the time of the first documented response (CR or PR) until disease progression (up to approximately 6 years)

Population: Intent-to-Treat (ITT) Population. Only participants with confirmed response by RECIST version 1.1 were included.

Overall response was defined as the percentage of confirmed responders (complete response \[CR\] + partial response \[PR\] per RECIST, Version 1.1) as summarized by Investigator assessment. CR was defined as the disappearance of all evidence of target lesions. PR was defined as at least a 30% reduction from Baseline in the sum of the longest diameter (LD) of all target lesions. Data were reported as those participants with measureable disease at Baseline.

Time frame: From randomization until the first documented complete response or partial response (up to approximately 6 years)

Population: Intent-to-Treat (ITT) Population. Only participants with measurable disease at baseline were included.

Progression-free survival (PFS) was defined as the interval of time between the date of randomization and the first documented occurrence of disease progression or death due to any cause. PFS for investigator-assessed response was summarized per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, which is a set of published rules defining when cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment. Disease progression was defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation.

Time frame: From randomization until the earliest date of disease progression (PD) or death due to any cause (up to approximately 6 years)

Population: Intent-to-Treat (ITT) Population.

Pre-treatment deaths were collected from screening visit up to the first day of treatment, for a maximum duration of 28 days. Patients who died during the screening period are considered as screen failure. On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 81.1 months (treatment duration ranged from 0.1 to 80.1 months). Deaths post treatment survival follow up were collected after the on- treatment period, up to approximately 6 years. Patients who didn't die during the on-treatment period and had not stopped study participation at the time of data cut-off (end of study) were censored.

Time frame: up to 28 days before Day 1 (Screening), up to 81.1 months (on-treatment), up to approximately 6 years (study duration)

Population: Clinical database population; all treated patients and patients who died during screening.