Highmark Commercial Medical Policy - Pennsylvania
Medical Policy: L-171-005
Topic: BRAF Testing for Melanoma Kinase Inhibitor Response
Section: Laboratory
Effective Date: November 13, 2017
Issue Date: November 13, 2017
Last Reviewed: March 2017

BRAF is part of a cell signaling pathway that helps control cell growth. Mutations in the BRAF gene can cause out of control cell growth, which may lead to cancer. The most common BRAF mutation is called V600E (previously known as V599E), which accounts for about 70-90% of mutations in this gene.

Targeted mutation analysis: Laboratories most commonly test for the BRAF V600E mutation, which accounts for about 90% of activating BRAF mutations. Mutation analysis requires relatively little tumor material for testing and has high sensitivity. It is also relatively inexpensive. BRAF mutation analysis is done on fresh, frozen, or paraffin-embedded tissue from either a primary tumor or metastasis. Some molecular diagnostic laboratories perform BRAF mutation analysis by laboratory-developed methods, while others use FDA-approved test kits. Laboratory-developed tests may vary in the specimen type required, methodology used, mutations tested, sensitivity, and other test-specific data.

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member’s benefit plan.

BRAF testing for melanoma kinase inhibitor response may be considered medically necessary when the following criteria are met:

 BRAF V600E tumor marker testing is not currently indicated as a companion diagnostic or for therapy selection for any other tumor types and is therefore not covered for these uses.

Procedure Codes
81210

Professional Statements and Societal Positions

The National Comprehensive Cancer Network (NCCN, 2016) includes vemurafenib, dabrafenib, dabrafenib in combination with trametinib, and vemurafenib in combination with cobimetinib as options for treatment of advanced or metastatic melanoma which require companion diagnostic testing. The guidelines state “For patients with BRAF-mutant metastatic disease. BRAFtargeted therapy first-line options include BRAF/MEK inhibitor combination therapy with dabrafenib/trametinib or vemurafenib/cobimetinib, or single-agent BRAF inhibitor therapy with vemurafenib/cobimetinib.”

The US Food and Drug Administration (FDA) approved each of these drugs with a companion diagnostic:

  • Zelboraf: "ZELBORAF® is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Limitation of Use: ZELBORAF is not indicated for treatment of patients with wild-type BRAF melanoma."
  • Tafinlar: “TAFINLAR is a kinase inhibitor indicated as a single agent for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. TAFINLAR in combination with trametinib is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. The use in combination is based on the demonstration of durable response rate. Improvement in disease-related symptoms or overall survival has not been demonstrated for TAFINLAR in combination with trametinib… Limitation of Use: TAFINLAR is not indicated for treatment of patients with wild-type BRAF melanoma."
  • Trametinib (Mekinist): "MEKINIST is a kinase inhibitor indicated as a single agent and in combination with dabrafenib for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. The use in combination is based on the demonstration of durable response rate. Improvement in disease-related symptoms or overall survival has not been demonstrated for MEKINIST in combination with dabrafenib…. MEKINIST as a single agent is not indicated for treatment of patients who have received prior BRAF-inhibitor therapy.”
  • Cotellic (cobimetinib): “COTELLIC is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib. Limitation of use: COTELLIC is not indicated for treatment of patients with wild-type BRAF melanoma.”

Place of Service: Outpatient

BRAF Testing for Melanoma Kinase Inhibitor Response is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.


The policy position applies to all commercial lines of business


Denial Statements

Services that do not meet the criteria of this policy will not be considered medically necessary. A network provider cannot bill the member for the denied service unless: (a) the provider has given advance written notice, informing the member that the service may be deemed not medically necessary; (b) the member is provided with an estimate of the cost; and (c) the member agrees in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.

A network provider cannot bill the member for the non-covered service.

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Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

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If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

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U.S. Department of Health and Human Services
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Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)

Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

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