Brief summary The purpose of this study is to compare how effective, encorafenib plus binimetinib is in the real-world and clinical trial settings. And produce results to show that combining data on encorafenib plus binimetinib from both the real-world and clinical trial settings is possible for future research studies.

This study group is identified from the database who:

• Have taken at least 1 order or administration of encorafenib plus binimetinib treatment after the confirmation of having metastatic melanoma after 27 June 2018.
• Are at least 18 years of age at the time of first encorafenib plus binimetinib initiation (index date).
• Had never received encorafenib plus binimetinib or had received first-line immunotherapy at the start of the study.
• Have ECOG status of 0 or 1 at the index date.
• have available data on the number of deaths in an area or group of people.

Patients will be followed from the date that the patient started the first encorafenib plus binimetinib treatment (treatment initiation) up to their last date of data availability. Last date of data availability could be the date of following events: patient lost to follow up at the clinic, death, or end of the database (January 2020). The database timeframe is June 2018 to January 2020.

Inclusion criteria:

• Diagnosis of melanoma (International Classification of Diseases 9th or 10th Revision Clinical Modification - ICD-9-CM: 172.X; ICD-10-CM: C43.x) and secondary malignancy or metastasis (ICD-9-CM: 196.x, 197.x, 198.x; ICD-10-CM: C77.x, C78.x, C79.x).
• Confirmed BRAF V600E/V600K activating mutation reported in the data based on laboratory or genetic analysis results.
• At least 1 order or administration of ENCO+BINI treatment

Exclusion criteria:

• Patients without information on mortality
• Patients with ECOG performance status ≥ 2 (at the time of randomization for patients from COLUMBUS, during the baseline period for patients in Flatiron Electronic Health Record)
• Patients with a history of or concurrent uveal or mucosal melanoma, basal cell or squamous cell carcinoma (as per trial inclusion criteria); this exclusion will also be applied to RWD patients

Patients with BRAF mutant + metastatic melanoma receiving encorafenib and binimetinib

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Eligible participants whose data was retrieved and observed in the study.

All cause mortality: COLUMBUS trial approximately 80.5 months and Flatiron EHR RWD approx 42.2 months. For adverse events it was not applicable as adverse event data was not planned to be collected.

This study is retrospective, it involves data that exist as structured data by the time of study start. The minimum criteria for reporting an adverse event (AE) (i.e., identifiable participant, identifiable reporter, a suspect product, and event) cannot be met. Hence, adverse events were not planned to be collected and are not reported.