ModifiedCapital BluecrossPolicy MP 2.364

Somatic Genetic Testing to Select Individuals with Melanoma or Glioma for Targeted Therapy or Immunotherapy (BRAF)

Defines medical necessity and investigational indications for somatic testing of BRAF variants and NTRK fusions in individuals with melanoma or glioma to select FDA‑approved targeted therapies; applies to Capital Bluecross products subject to benefit variations.

Policy Summary

PayerCapital Bluecross

PolicySomatic Genetic Testing to Select Individuals with Melanoma or Glioma for Targeted Therapy or Immunotherapy (BRAF)

Policy CodePolicy MP 2.364

Change TypeMaterial coverage revisions and coding updates

Effective DateSep 1, 2025

Next Review Date

Key ActionObtain prior authorization per member benefit and submit appropriate procedure and diagnosis codes (e.g., C43.*, C71.*) to support medical necessity.

SourceLink

POLICY UPDATE CHANGES

Added criteria for NTRK fusion testing in cutaneous melanoma to allow either tissue or liquid biopsy.

Testing for BRAF V600 variants for glioma changed from investigational to medically necessary for treatment with dabrafenib plus trametinib.

Tumor Mutational Burden (TMB) criteria removed from this policy and placed into MP 2.388.

Added new CPT/PLA code 0473U to the policy coding list.

NCCN 2A+Evidence basis

50-70%BRAF in melanoma

80%

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BRAF V600E proportion

0473U, 81191-94Procedure codes listed

C43.*, C71.*ICD-10 examples

Coverage Criteria

Medical necessity and investigational indications

Covered when ALL of the following are met for specified indications:

Melanoma: unresectable/metastatic or resected stage III: Testing for BRAF V600 variants in individuals with unresectable or metastatic melanoma, or with resected stage III melanoma is medically necessary to select individuals for treatment with FDA‑approved BRAF inhibitors or MEK inhibitors.

See Policy Guidelines for companion diagnostics and NCCN/FDA guidance.

Melanoma: other situations: Testing for BRAF V600 variants for all other individuals with melanoma is considered investigational and not supported by sufficient evidence.

Insufficient evidence for benefit.

Glioma: BRAF for dabrafenib+trametinib: Testing for BRAF V600E variants in individuals with glioma is medically necessary to select individuals for targeted treatment with dabrafenib in combination with trametinib.

Testing for BRAF V600 variants for other glioma indications to select targeted treatment is investigational.

NTRK fusions in melanoma: Testing for NTRK gene fusions in individuals with unresectable or metastatic melanoma is medically necessary to select individuals for treatment with FDA‑approved kinase inhibitors.

Testing for NTRK fusions to select non‑FDA approved targeted therapies is investigational.

NTRK fusions in glioma: Testing for NTRK gene fusions in individuals with glioma is medically necessary to select individuals for treatment with FDA‑approved kinase inhibitors.

Testing for NTRK fusions to select non‑FDA approved targeted therapies is investigational.

Medically necessary coverage for somatic genetic testing

Covered when testing is to select individuals with melanoma or glioma for FDA‑approved targeted therapies with supporting NCCN recommendations (2A or higher).

BRAF testing for melanoma: BRAF gene variant testing to select treatment with FDA‑approved targeted therapy for individuals with melanoma is supported by FDA approvals and NCCN recommendations (2A or higher).

Evidence includes pivotal studies leading to FDA and NCCN recommendations.

BRAF testing for glioma: BRAF gene variant testing to select treatment with FDA‑approved targeted therapy for glioma is supported by FDA approvals and NCCN recommendations; testing for BRAF V600E for treatment with dabrafenib plus trametinib is listed as medically necessary.

Policy history documents change from investigational to medically necessary for glioma BRAF V600E (see policy history).

NTRK fusion testing: NTRK gene fusion testing to select treatment with FDA‑approved targeted therapy for melanoma and glioma is supported by FDA approvals and NCCN recommendations; for cutaneous melanoma testing may be performed on tissue or liquid biopsy as per recent revision to policy guidelines.

This policy does not address the use of BRAF testing for the purpose of CNS (central nervous system) tumor diagnosis. For guidance on testing indications not listed here, refer to MP 2.259 Expanded Molecular Panel Testing of Cancers to Identify Targeted Therapies and current FDA/NCCN resources.

Testing for tumor mutational burden (TMB) in individuals with unresectable or metastatic melanoma or glioma to select individuals for treatment with FDA‑approved immunotherapy is considered investigational and is not covered under this policy. The TMB criteria and related coding have been moved to policy MP 2.388.

Testing for BRAF V600 variants for all other individuals with melanoma or glioma (that do not meet the specified medically necessary indications such as unresectable/metastatic or resected stage III melanoma, or glioma eligible for dabrafenib plus trametinib) is considered investigational and is not supported due to insufficient evidence.

NOT COVERED: BRAF testing to select targeted therapy for melanoma or glioma when used outside the medically necessary indications listed in this policy is not covered. Additionally, NTRK testing to select treatments that are not FDA‑approved kinase inhibitors for the specified indications is considered investigational and not covered. Procedure code 0037U is specifically listed as investigational and not covered when used for TMB testing.

NOT COVERED: Testing for tumor mutational burden (TMB) to select patients for immunotherapy is not covered under this policy; TMB criteria have been administratively removed from MP 2.364 and relocated to MP 2.388. The policy coding list identifies procedure code 0037U as investigational when used for TMB.

Covered Indications

Individuals with unresectable or metastatic melanoma, or resected stage III melanoma — BRAF V600 testing to select FDA‑approved BRAF or MEK inhibitors.

Indication: Individuals with unresectable or metastatic melanoma, or with resected stage III melanoma who are being considered for FDA‑approved BRAF or MEK inhibitors.

Testing is to identify BRAF V600 variants to guide selection of FDA‑approved targeted therapy.

Clinical requirement: Specimen types and testing methods (single‑gene assay or panel) acceptable per Policy Guidelines; companion diagnostics per FDA/NCCN may be used.

Laboratory‑developed tests must meet CLIA high‑complexity standards.

Individuals with glioma — BRAF V600E testing to select dabrafenib in combination with trametinib (where applicable).

Indication:

Coding

FDA-approved drugs and companion diagnostics referencedmixed

No codes listed

Covered when medically necessaryCPTCovered

0473U	Procedure code listed in policy
81191	Procedure code listed in policy
81192	Procedure code listed in policy
81193	Procedure code listed in policy
81194	Procedure code listed in policy
81210	Procedure code listed in policy

Investigational / not covered for TMBCPTNot Covered

0037U

Procedure code considered investigational / not covered when used for tumor mutational burden (TMB)

Relevant diagnosis codesICD-10

C43.0	Malignant melanoma of lip
C43.10	Malignant melanoma of unspecified eyelid, including canthus
C43.111	Malignant melanoma of right upper eyelid, including canthus
C43.112	Malignant melanoma of right lower eyelid, including canthus
C43.121	Malignant melanoma of left upper eyelid, including canthus
C43.122	Malignant melanoma of left lower eyelid, including canthus
C43.20	Malignant melanoma of unspecified ear and external auricular canal
C43.21	Malignant melanoma of right ear and external auricular canal
C43.22	Malignant melanoma of left ear and external auricular canal
C43.30	Malignant melanoma of unspecified part of face

1–10 of 34

1/4

Tumor mutational burden (TMB) definition

TMB-H threshold>= 10 mutations/megabase (TMB‑H defined as 10 mutations/megabase)

Context of useTumor mutational burden referenced for selection of immunotherapy indications in policy history

Coding noteProcedure code 0037U is listed as investigational and not covered when used for TMB

Investigational use — TMB

Coverage stanceTMB testing to select individuals for immunotherapy is considered investigational and not covered under this policy (criteria moved to MP 2.388)

Policy relocation

Provider Actions & Billing Guidance

Prior Authorization

Product- and program-specific prior authorization

Product- and program-specific prior authorization may apply. Coverage depends on the member's benefit program and the presence of a listed code does not guarantee coverage. If a requested test is not listed in this policy, refer to MP 2.259 Expanded Molecular Panel Testing of Cancers to Identify Targeted Therapies for additional guidance.

Policy applicability varies by Capital BlueCross product and program; verify member benefits and prior authorization requirements before ordering.
The identification of a code in the coding section does not denote coverage; eligibility is determined by the member's benefit information.
For tests not listed in this policy, see MP 2.259 for guidance on expanded molecular panel testing.

Documentation Required

Coding and diagnosis documentation

Submit appropriate procedure and diagnosis codes to support medical necessity. Provide documentation that demonstrates the applicable clinical indication (for example, unresectable or metastatic melanoma, resected stage III melanoma, or glioma when selecting patients for dabrafenib + trametinib).

Eligibility Requirements

ELIGIBILITY REQUIREMENTS: See the policy coverage criteria for the specific medically necessary indications. Coverage is limited to individuals who meet the stated clinical scenarios in the policy (for example, unresectable or metastatic melanoma, resected stage III melanoma, or glioma candidates for dabrafenib plus trametinib) and when testing is performed to select FDA‑approved targeted therapies supported by NCCN recommendations.

ELIGIBILITY REQUIREMENTS: There are no additional top‑level eligibility nodes specified in this policy beyond the clinical indications described in the coverage criteria. If coverage of a test or indication is requested but not addressed here, refer to MP 2.259 for guidance.

Background

Background: BRAF is a proto‑oncogene encoding a serine/threonine kinase that, when altered (commonly at codon V600, e.g., V600E, V600K), results in constitutive activation of the RAF‑MEK‑ERK signaling pathway. These activating variants are targetable with BRAF and MEK inhibitors, and testing for BRAF V600 variants is used to identify patients with melanoma or certain gliomas who may benefit from FDA‑approved targeted therapies.

Definitions

BRAF — definition and variant notes

GeneBRAF (b-raf proto-oncogene, serine/threonine kinase)

Common actionable variantsV600E and V600K (the majority of BRAF-variant melanomas are V600E; ~16% are V600K)

Clinical relevanceBRAF V600 variants produce constitutive kinase activity and can be targeted by BRAF and MEK inhibitors to select FDA-approved therapies for melanoma and, where specified, glioma

NTRK — definition and clinical relevance

Gene/fusionNTRK (neurotrophic tyrosine receptor kinase) gene fusions

FDA‑approved therapiesLarotrectinib (Vitrakvi) and Entrectinib (Rozlytrek) are approved for NTRK fusion–positive solid tumors

Policy Summary

PayerCapital Bluecross

PolicySomatic Genetic Testing to Select Individuals with Melanoma or Glioma for Targeted Therapy or Immunotherapy (BRAF)

Policy CodePolicy MP 2.364

Change TypeMaterial coverage revisions and coding updates

Effective DateSep 1, 2025

Next Review Date

Key ActionObtain prior authorization per member benefit and submit appropriate procedure and diagnosis codes (e.g., C43.*, C71.*) to support medical necessity.

SourceLink

On This Page

Companion diagnostics (e.g., FoundationOne CDx, FoundationOne Liquid CDx) are referenced in relation to FDA approvals.

Individuals with glioma being considered for targeted treatment with dabrafenib in combination with trametinib when a BRAF V600E variant is present.

Policy history updated 11/07/2023: glioma BRAF V600E testing changed from investigational to medically necessary for dabrafenib plus trametinib.

Limitations: BRAF testing for glioma to select other targeted treatments (not dabrafenib plus trametinib) remains investigational.

See Policy Guidelines for diagnostic role exclusions (policy does not address BRAF testing for CNS tumor diagnosis).

Individuals with unresectable or metastatic melanoma or glioma — NTRK fusion testing to select FDA‑approved kinase inhibitors (e.g., larotrectinib, entrectinib) when clinically indicated.

Indication: Individuals with unresectable or metastatic melanoma or individuals with glioma may be tested for NTRK gene fusions when testing is being used to select treatment with FDA‑approved kinase inhibitors (e.g., larotrectinib, entrectinib).

FDA approvals and NCCN recommendations (2A or higher) support use; companion diagnostics are noted in FDA labeling.

Specimen and method: Testing may be performed by validated single‑gene assays or as part of multigene panels; policy guidelines updated to permit tissue or liquid biopsy for NTRK testing in cutaneous melanoma.

Refer to Policy Guidelines and MP 2.259 for expanded panels and test selection.

Somatic testing (BRAF, NTRK) to select patients with melanoma or glioma for FDA‑approved targeted therapies (including dabrafenib plus trametinib for BRAF V600E glioma).

Scope: Somatic testing (BRAF, NTRK) is indicated to select patients with melanoma or glioma for FDA‑approved targeted therapies, including dabrafenib plus trametinib for BRAF V600E glioma.

Supported by FDA approvals and NCCN recommendations (2A or higher); evidence includes pivotal studies leading to approvals.

Testing modalities: Appropriate testing modalities include single‑gene assays, multigene panels, and validated companion diagnostics; laboratory‑developed tests must meet CLIA requirements.

See MP 2.259 for guidance on expanded molecular panel testing.

TMB criteria were removed from this policy and placed in MP 2.388

Investigational procedure codeProcedure code 0037U is investigational and not covered when used for tumor mutational burden (TMB)

Include relevant ICD-10 diagnosis codes (examples: C43.* for malignant melanoma; C71.* for malignant neoplasm of cerebrum) on claims and supporting documentation.
Attach pathology, staging, and treatment intent documentation as needed to substantiate medical necessity for BRAF or NTRK testing.
Note: Code lists in the Coding Information section are not exhaustive and are subject to change.

Denial Risk

Investigational indications and coverage limitations

Testing for BRAF V600 variants outside the medically necessary indications described in this policy is considered investigational and may be denied. Coverage is contingent on meeting the clinical criteria specified in the policy and on member benefit provisions.

Investigational indications (e.g., BRAF testing for melanoma or glioma patients not meeting the policy's specified indications) are subject to denial.
Presence of an applicable CPT/HCPCS code does not guarantee payment; confirm benefits and obtain prior authorization if required.

Billing Rule

Provider Actions

Provider actions (billing and submission): ensure claim submission includes the procedure code(s), appropriate ICD-10 diagnosis code(s), and supporting clinical documentation. If prior authorization is required by the member's plan, obtain approval before testing to avoid claim denial.

Verify member benefit coverage and prior authorization requirements prior to specimen submission.
Submit all relevant clinical documentation (diagnosis, stage, prior therapies, and treatment plan) to support medical necessity.
Follow Capital BlueCross product-specific billing rules and coding guidance; when in doubt, contact Provider Services or refer to the member's plan documents.

Clinical useNTRK fusion testing may be used to select individuals with melanoma or glioma for FDA‑approved kinase inhibitors when clinically indicated

Definitions — NA

PlaceholderNot available (NA)

NoteNo additional definition text provided in source

UsageRetained as an NA placeholder for undefined terms in this policy