Real-World Patient Characteristics, Treatment Patterns, and Clinical Outcomes Among Patients With BRAF-Positive Metastatic Melanoma

This was a retrospective, longitudinal, observational study conducted using the Flatiron Health electronic health record (EHR)-derived database. BRAF+ advanced or metastatic (i.e., stage III or IV) melanoma patients treated at oncology practices across the US were identified for potential inclusion. All included patients were aged ≥18 years and required to have a diagnosis of melanoma (International Classification of Diseases (ICD)-9 172.x & ICD-10 C43 or D03x), a pathologic unresectable stage III or IV diagnosis, subsequent first-line (1L) treatment with either immunotherapy (IO) (nivolumab, pembrolizumab, ipilimumab + nivolumab) or targeted therapy (TT) dafratenib + trametinib (dab/tram) on or after 01 January 2014, and evidence of a BRAF-positive result at any point in time.

Study Overview

• Status: Completed
• Conditions: BRAF-positive Metastatic Melanoma

• Study Type: Observational
• Enrollment (Actual): 785

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • East Hanover, New Jersey, United States, 07936
      • Novartis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This was a retrospective, noninterventional cohort study.

Description

Inclusion criteria:

• Diagnosis of melanoma (ICD-9 172x & ICD-10 C43 or D03x)
• ≥2 documented clinical encounters on different days in the Flatiron network on or after 01 January 2011
• Pathologic unresectable stage III or IV at initial diagnosis after 01 January 2011, or earlier stage disease accompanied by development of a first locoregional recurrence after 01 January 2011
• Diagnosis of MM after 01 January 2011
• Evidence of a BRAF-positive result at any point in time

• Treatment with one of the following 1L therapies on or after 01 January 2014:

  • IO (nivolumab, pembrolizumab, or ipilimumab + nivolumab)
  • TT (dab/tram)
• At least 18 years of age at the time of initiation of 1L therapy
• At least 6-months of continuous follow-up from the time of initiation of 1L therapy

Exclusion Criteria:

• Lacking relevant unstructured documents (i.e., information such as free text from a physician note or pathology report that is captured systematically during the data abstraction process) in the Flatiron Health database
• Evidence of non-skin melanoma (ocular, subungual, mucosal, palmar, plantar)
• Documented receipt of a clinical study drug, defined as any uncancelled order, administration, or oral episode for a clinical study drug for cancer at any time prior to or during 1L treatment
• Presence of leptomeningeal disease (ICD-9 198.4 & ICD-10 C79.32 or C79.49)

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
Patients with high tumor burden (HTB)
Patients with low tumor burden (LTB)
Patients with central nervous system (CNS) metastases
Patients with without CNS metastases
1L IO-refractory patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean age of 1L dab/tram-treated BRAF+ MM patients		Baseline
Number and percentage of 1L dab/tram-treated BRAF+ MM patients who identify per sex		Baseline
Number and percentage of 1L dab/tram-treated BRAF+ MM patients per race category		Baseline
Number and percentage of 1L dab/tram-treated BRAF+ MM patients per ethnicity category		Baseline
Number and percentage of 1L dab/tram-treated BRAF+ MM patients per geographic region		Baseline
Number and percentage of 1L dab/tram-treated BRAF+ MM patients per type of medical practice		Baseline
Number and percentage of 1L dab/tram-treated BRAF+ MM patients per insurance type		Baseline
Number and percentage of 1L dab/tram-treated BRAF+ MM patients with an Eastern Cooperative Oncology Group (ECOG) score of 0, 1, 2, 3, or 4	ECOG performance status describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). Scores can range from a lower value of 0 (fully active, able to carry on all pre-disease performance without restriction) up to 5 (dead).	Baseline
Number and percentage of 1L dab/tram-treated BRAF+ MM patients per location of metastatic site		Baseline
Alanine aminotransferase (ALT) levels in 1L dab/tram-treated BRAF+ MM patients		Baseline
Aspartate aminotransferase (AST) levels in 1L dab/tram-treated BRAF+ MM patients		Baseline
Lactate dehydrogenase (LDH) levels in 1L dab/tram-treated BRAF+ MM patients		Baseline
Number and percentage of 1L dab/tram-treated BRAF+ MM patients treated with 2L therapy		Up to approximately 2 years
Time from the start of 1L dab/tram therapy until the start of 2L therapy		Up to approximately 2 years
Real-world progression-free survival (rwPFS) for 1L dab/tram-treated BRAF+ MM patients	rwPFS was defined as the time from the start of 1L dab/tram therapy until first progression or death from any cause.	Up to approximately 2 years
Overall survival (OS) for 1L dab/tram-treated BRAF+ MM patients	OS was defined as the time from the start of 1L dab/tram therapy until death from any cause.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean age of 1L IO-refractory patients with BRAF+ MM		Baseline
Number and percentage of 1L IO-refractory patients with BRAF+ MM who identify per sex		Baseline
Number and percentage of 1L IO-refractory patients with BRAF+ MM per race category		Baseline
Number and percentage of 1L IO-refractory patients with BRAF+ MM per ethnicity category		Baseline
Number and percentage of 1L IO-refractory patients with BRAF+ MM per geographic region		Baseline
Number and percentage of 1L IO-refractory patients with BRAF+ MM per type of medical practice		Baseline
Number and percentage of 1L IO-refractory patients with BRAF+ MM per insurance type		Baseline
Number and percentage of 1L IO-refractory patients with BRAF+ MM with an ECOG score of 0, 1, 2, 3, or 4	ECOG performance status describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). Scores can range from a lower value of 0 (fully active, able to carry on all pre-disease performance without restriction) up to 5 (dead).	Baseline
Number and percentage of 1L IO-refractory patients with BRAF+ MM per location of metastatic site		Baseline
Alanine aminotransferase (ALT) levels in 1L IO-refractory patients with BRAF+ MM		Baseline
Aspartate aminotransferase (AST) levels in 1L IO-refractory patients with BRAF+ MM		Baseline
Lactate dehydrogenase (LDH) levels in 1L IO-refractory patients with BRAF+ MM		Baseline
Time from the first disease progression until next disease progression in 1L IO-refractory patients with BRAF+ MM		Up to approximately 2 years
Number and proportion of patients remaining on 1L IO therapy following disease progression		Up to approximately 2 years
Time patients remained on 1L IO therapy following disease progression		Up to approximately 2 years
Number and percentage of patients treated with 2L therapy, overall and by therapy type		Up to approximately 2 years
Time from the start of 1L IO until the start of 2L therapy		Up to approximately 2 years
Time from the first disease progression until the start of 2L therapy		Up to approximately 2 years
rwPFS for 1L IO-refractory patients with BRAF+ MM	rwPFS was defined as the time from the first disease progression until next progression or death from any cause.	Up to approximately 2 years
OS for 1L IO-refractory patients with BRAF+ MM	OS was defined as the time from the first disease progression until death from any cause.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2022
• Primary Completion (Actual): November 1, 2022
• Study Completion (Actual): November 24, 2022

Study Registration Dates

• First Submitted: February 1, 2024
• First Submitted That Met QC Criteria: February 1, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Actual): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: CTMT212AUS66