Premera Bluecross BRAF MEK Coverage Update

Coverage and Medical Necessity Criteria

inv-01: Combination therapy — melanoma

Combination regimens covered when specific mutation and disease-state criteria are met

Melanoma combination therapy: Braftovi (encorafenib) + Mektovi (binimetinib), Tafinlar (dabrafenib) + Mekinist (trametinib), or Zelboraf (vemurafenib) + Cotellic (cobimetinib) may be considered medically necessary for unresectable or metastatic melanoma with a BRAF V600E or V600K mutation.mutation: BRAF V600E or V600K

Testing for BRAF V600 mutations is covered whenever use of BRAF inhibitors is contemplated.

inv-02: Combination therapy — colorectal cancer

Combination regimens covered for metastatic colorectal cancer with BRAF V600E

Metastatic colorectal cancer: Braftovi (encorafenib) + Erbitux (cetuximab), and Braftovi in combination with Erbitux and fluorouracil-based chemotherapy may be considered medically necessary for metastatic colorectal cancer with a BRAF V600E mutation in individuals aged 18 years or older after prior therapy.age >=18; mutation: BRAF V600E

Two‑agent regimen requires prior therapy; chemotherapy backbone described as fluorouracil‑based per policy update.

inv-03: Combination therapy — NSCLC

Combination regimens covered for NSCLC with BRAF V600E

NSCLC: Braftovi (encorafenib) + Mektovi (binimetinib) may be considered medically necessary for metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation in individuals aged 18 years or older.age >=18; mutation: BRAF V600E

Encorafenib + binimetinib indication added for certain adults with metastatic NSCLC in 2024 update.

inv-04: Other combination and monotherapy indications

Other indicated combination and monotherapy uses

Ovarian LGSOC: Avmapki (avutometinib) + Fakzynja (defactinib) may be considered medically necessary for KRAS‑mutated recurrent low‑grade serous ovarian cancer in individuals aged 18 years or older who have received at least 1 prior platinum‑based regimen.age >=18; KRAS‑mutated; prior platinum‑based regimen

Added to policy history in 2025.

Tafinlar + Mekinist other uses: Tafinlar (dabrafenib) + Mekinist (trametinib) may be considered medically necessary for: adjuvant melanoma with BRAF V600E or V600K and nodal involvement after complete resection; metastatic NSCLC with BRAF V600E; locally advanced or metastatic anaplastic thyroid cancer with BRAF V600E and no satisfactory locoregional options; unresectable/metastatic solid tumors (adult and pediatric >=1 year) with BRAF V600E after prior treatment with no satisfactory alternatives; and pediatric (1–17 years) low‑grade glioma with BRAF V600E who require systemic therapy.age and mutation criteria vary by indication

Testing for BRAF V600 mutations is covered whenever BRAF inhibitors are contemplated.

inv-05: General coverage determinations

Coverage stance

Not medically necessary: Use of BRAF and/or MEK inhibitors for treatment of individuals with wild‑type BRAF is considered not medically necessary.BRAF wild‑type

Requests for BRAF/MEK inhibitors in wild‑type BRAF may be denied.

Investigational uses: All other uses of the medications listed in this policy are considered investigational.unspecified

Medications are subject to the product's FDA dosage and administration prescribing information.

inv-06: Length of approval

Approval duration and reauthorization

Approval duration: Initial non‑formulary exception reviews and other initial authorizations for drugs listed in the policy may be approved up to 12 months; for oral drugs the initial authorization period was updated to 6 months as noted in the policy history.up to 12 months (initial non‑formulary exception reviews); oral drug initial auth = 6 months per 2026 update

Re‑authorization may be approved up to 12 months if drug‑specific criteria are met and chart notes document continued positive clinical response.

inv-07: New and updated covered indications

Policy additions and covered indications added in updates are as follows

tovorafenib (Ojemda): Covered for pediatric individuals >=6 months and <18 years with relapsed or refractory pediatric low‑grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.age >=6 months and <18 years; documented BRAF fusion/rearrangement or V600 mutation

Added in 2024 and summarized in subsequent history entries.

mirdametinib (Gomekli): Covered for individuals with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas; policy requires trial and inadequate response or intolerance to selumetinib (Koselugo) or documentation of inability to swallow selumetinib before coverage.prior inadequate response/intolerance to selumetinib where applicable; age >=2 years per original listing

Added in 2025 and criteria refined in 2026 to require prior selumetinib trial.

encorafenib + binimetinib (Braftovi + Mektovi):

Use of BRAF and/or MEK inhibitors for individuals with wild-type BRAF is considered not medically necessary. Requests for these agents when the tumor is documented as BRAF wild-type should be denied as not medically necessary.

Coverage of medications in this policy is subject to the member's benefit booklet limitations and the product's FDA dosage and administration prescribing information. The policy statements do not apply to Medicare Advantage plans. Reviewers should verify benefit applicability and confirm dosing/administration against the current FDA label when making coverage determinations.

Use of BRAF and/or MEK inhibitors for the treatment of individuals with documented wild-type BRAF is classified as not medically necessary. Coverage is reserved for situations where the presence of an actionable BRAF alteration (as specified in individual drug criteria) is documented in the medical record.

Member contracts vary; coverage decisions must align with the provisions of the member's benefit booklet. Where the policy designates a use as not medically necessary, that determination applies unless the member's contract language provides otherwise. Additionally, initial authorization lengths and exception approvals follow the policy's stated limits (see length of approval and exception rules).

Definitions and Background

BRAF and MEK are kinases in the MAPK-ERK signaling pathway. Activating BRAF mutations, most commonly V600E and V600K, cause constitutive pathway activation that drives tumor growth in multiple cancers. Inhibitors targeting BRAF and downstream MEK reduce MAPK-ERK signaling and have demonstrated clinical benefit in appropriately selected patients with BRAF-activating alterations.

BRAF V600E mutation

DefinitionBRAF V600E: substitution of glutamic acid for valine at amino acid position 600 leading to constitutive activation of the MAPK-ERK signaling pathway.

Prevalence among BRAF mutationsRepresents approximately 90%–95% of known BRAF mutations in human cancer.

Biologic consequenceMutated BRAF causes constitutive MAPK-ERK signaling resulting in tumor maintenance and progression.

Clinical relevanceBRAF mutation may be a negative prognostic indicator in metastatic melanoma.

Initial Therapy Coverage Rules

inv-24: Initial therapy rules

Initial coverage criteria for listed drugs

Encorafenib + binimetinib initial: Encorafenib (Braftovi) + binimetinib (Mektovi) may be considered medically necessary for unresectable or metastatic melanoma with a BRAF V600E or V600K mutation.mutation: BRAF V600E or V600K

Testing for BRAF V600 mutations is covered whenever use of BRAF inhibitors is contemplated.

Dabrafenib + trametinib initial: Dabrafenib (Tafinlar) + trametinib (Mekinist) may be considered medically necessary for multiple indications including unresectable or metastatic melanoma with BRAF V600E or V600K, specified NSCLC and anaplastic thyroid cancer with BRAF V600E, unresectable/metastatic solid tumors with BRAF V600E (adult and pediatric >=1 year) after prior treatment with no satisfactory alternatives, and pediatric low‑grade glioma with BRAF V600E who require systemic therapy.age and mutation criteria vary by indication

Refer to indication‑specific statements in the policy for age and prior therapy requirements.

Continuation, Reauthorization, and Re-induction

inv-26: Continuation therapy / reauthorization

Re‑authorization criteria

Re-authorization: Re‑authorization may be approved up to 12 months as long as drug‑specific coverage criteria are met and chart notes demonstrate continued positive clinical response to therapy.documented clinical benefit

Initial authorization periods vary; oral drugs initial auth updated to 6 months per 2026 history.

inv-27: Re-induction guidance

Re‑induction guidance per NCCN

re-induction BRAF/MEK: Re‑induction therapy may be considered for individuals who previously achieved disease control (complete response, partial response, or stable disease) with no residual toxicity and who later experience disease progression more than three months after treatment discontinuation.progression >3 months after discontinuation

Step Therapy Requirements

Step	Indication	Required prior therapy / condition	Coverage status
1
Metastatic colorectal cancer with documented BRAF V600E mutation in individuals aged 18 years or older
Prior therapy required before Braftovi (encorafenib) + Erbitux (cetuximab) two‑agent regimen; option to use Braftovi + Erbitux + fluorouracil‑based chemotherapy per label
Covered with criteria

Step	Indication	Required prior therapy / condition	Coverage status
1
Symptomatic, inoperable plexiform neurofibromas in individuals with neurofibromatosis type 1
Prior trial of selumetinib (Koselugo) with inadequate response or intolerance required before coverage of mirdametinib (Gomekli)
Covered with criteria

Provider Requirements, Documentation, and Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required. Documentation must demonstrate that the drug‑specific coverage criteria are met. Initial authorizations for oral drugs listed in this policy may be approved for up to 6 months; non‑formulary exception reviews for all drugs listed in the policy may be approved up to 12 months. Reauthorization may be approved up to 12 months provided documentation shows continued clinical benefit and that coverage criteria remain met.

Initial authorizations for oral drugs: up to 6 months
Non‑formulary exception approvals: up to 12 months
Reauthorizations: up to 12 months with documented ongoing benefit

Denial Risk

Denial Risk for Non‑label or Non‑formulary Use

Requests that are inconsistent with the product's FDA dosing and administration, that exceed indicated populations, or that seek use in individuals with wild‑type BRAF may be denied. Non‑formulary exception approvals are limited and require meeting the noted exception criteria.

Coding

Codingmixed

No codes listed

Site of Care and Benefit Application

Note

Manage drugs via the pharmacy benefit

These medications are managed through the pharmacy benefit; there are no site-of-care restrictions specified in this portion of the policy.

Billing Rule

Oral agents follow outpatient pharmacy benefit and product labeling

Oral agents are covered under the outpatient/ambulatory pharmacy benefit and must be dosed and monitored according to the product labeling.

Follow product labeling for dosing and monitoring

OpenPayer

BRAF and MEK Inhibitors (Pharmacy Coverage Criteria)