||BRAF Testing for Melanoma Kinase Inhibitor Response
||November 13, 2017
||November 13, 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:
- Individual has been diagnosed with metastatic or unresectable melanoma; and
- At least ONE of the following treatment is being considered: Zelboraf® (vemurafenib), Tafinlar® (dabrafenib), Mekinist® (trametinib) in combination with Tafinlar® (dabrafenib), or Zelboraf® (vemurafenib) in combination with Cotellic® (cobimetinib); and
- BRAF V600 testing has not been performed previously.
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.
|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|
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.
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.
Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:
If you need these services, contact the Civil Rights Coordinator.
- Provides free aids and services to people with disabilities to communicate effectively with us, such as:
- Qualified sign language interpreters
- Written information in other formats (large print, audio, accessible electronic formats, other formats)
- Provides free language services to people whose primary language is not English, such as:
- Qualified interpreters
- Information written in other languages
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.
You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:
U.S. Department of Health and Human Services
200 Independence Avenue, SW
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.
Insurance or benefit/claims administration may be provided by Highmark, Highmark Choice Company, Highmark Coverage Advantage, Highmark Health Insurance Company, First Priority Life Insurance Company, First Priority Health, Highmark Benefits Group, Highmark Select Resources, Highmark Senior Solutions Company or Highmark Senior Health Company, all of which are independent licensees of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield plans.
Highmark retains the right to review and update its medical policy guidelines at its sole discretion. These guidelines are the proprietary information of Highmark. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.