CurrentPremera BluecrossPolicy N/A

BRAF and MEK Inhibitors

Pharmacy benefit policy describing medical necessity coverage criteria, indications, exclusions, documentation and approval lengths for BRAF and MEK inhibitors and specific combinations across melanoma, colorectal cancer, NSCLC, ovarian cancer, NF1, pediatric LGG and other listed indications.

Policy Summary

PayerPremera Bluecross

PolicyBRAF and MEK Inhibitors

Policy CodePolicy N/A

Change TypeReviewed; no coverage changes

Effective DateMar 1, 2026

Next Review Date

Key ActionInclude BRAF V600 mutation test results in the medical record submitted for review.

POLICY UPDATE CHANGES

Reviewed prescribing information for all drugs in the policy and reviewed NCCN guideline; no clinical policy statement changes for 03/01/26 update.

Prior updates (2019-2025) added multiple drug-specific indications including Braftovi+Erbitux+mFOLFOX6 for metastatic CRC, Ojemda for pediatric LGG, Gomekli for NF1, Avmapki+Fakzynja for KRAS-mutated LGSOC and expanded pediatric age ranges for selumetinib.

MultipleCovered indications (agents/combinations)

12+Drugs/combinations referenced

1Not medically necessary (wild-type BRAF)

Coverage Summary & Scope

Scope: Pharmacy benefit policy describing medical necessity coverage criteria, indications, exclusions, documentation and approval lengths for BRAF and MEK inhibitors and specific combinations across melanoma, colorectal cancer, NSCLC, ovarian cancer, NF1, pediatric LGG and other listed indications.

Coverage stance: mixed — the policy specifies multiple covered (medically necessary) indications and also lists not medically necessary and investigational uses.

Background: BRAF and MEK inhibitors target MAPK pathway activation due to BRAF mutations (primarily V600E/V600K), blocking constitutive MAPK-ERK signaling that drives tumor growth and predicting response to these agents.

Effective date: Mar. 1, 2026; Last review: Feb. 23, 2026.

Combination therapy for metastatic colorectal cancer (medically necessary)

Covered when ALL of the following are met:

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Tafinlar + Mekinist: Other combination indications (medically necessary)

Other combination indications for Tafinlar + Mekinist (medically necessary)

Covered when ALL of the following are met (per listed bullet indications):

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Neurofibromatosis type 1 therapies (medically necessary)

Gomekli (mirdametinib) for NF1 (medically necessary)

Covered when ALL of the following are met:

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Koselugo (selumetinib) for NF1 (medically necessary)

Covered when ALL of the following are met:

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Not Medically Necessary & Investigational / Unproven

Not medically necessary

The following uses are considered not medically necessary:

ref

Investigational/Unproven

All other uses not listed as medically necessary are considered investigational.

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Provider Actions & Prior Authorization

Documentation Required

BRAF V600 mutation test result required

For BRAF inhibitors, include test results showing the presence of BRAF V600 mutations in the medical record submitted for review. Examples of acceptable test evidence include mutation testing results demonstrating BRAF V600E or V600K by an approved molecular method (for example, PCR, next-generation sequencing, or other validated assay).

Pathology/molecular report showing BRAF V600E or V600K
Next-generation sequencing (NGS) report identifying BRAF V600 mutation
PCR-based mutation test result indicating BRAF V600 mutation

Prior Authorization

Pharmacy benefit management / prior authorization

Drugs in this policy are managed through the pharmacy benefit. Non-formulary exception reviews for drugs listed in this policy may be approved for up to 12 months. Other reviews may also be approved for up to 12 months if the criteria are met and chart notes demonstrate continued positive clinical response.

Documentation Required

Medical records must demonstrate criteria met

The individual’s medical records submitted for review must document that the stated medical necessity criteria are met. Chart notes should demonstrate that the individual meets the criteria for the requested indication and support ongoing clinical response when seeking authorization or re-authorization.

Chart notes demonstrating that the individual meets the stated criteria for medical necessity
Documentation of continued positive clinical response for re-authorization

Clinical Evidence Summary

14.9 moCOLUMBUS (encorafenib+binimetinib) — median PFS 14.9 vs 7.3 months (vemurafenib)

11.4 moCOMBI-d/COMBI-v (dabrafenib+trametinib) — median PFS 11.4 vs 7.3 months; demonstrated overall survival benefit

12.3 moVemurafenib+cobimetinib — median PFS 12.3 vs 7.2 months (vemurafenib)

51%FIREFLY-1 (tovorafenib) — ORR 51% in relapsed/refractory pediatric LGG

Supporting evidence highlights: Avutometinib + defactinib (RAMP 201) demonstrated a confirmed overall response rate of 44% in 57 patients with KRAS-mutated recurrent low-grade serous ovarian cancer who had received prior systemic therapy including platinum-based chemotherapy.

Other pivotal trial results summarized in the policy include encorafenib + binimetinib (COLUMBUS), dabrafenib + trametinib (COMBI-d/COMBI-v), vemurafenib + cobimetinib, and tovorafenib (FIREFLY-1) for pediatric LGG, as reviewed in the Evidence Review.

Guideline and prescribing information review: The policy notes that prescribing information for all drugs in the policy and NCCN guideline recommendations were reviewed for the 03/01/26 update and that no clinical policy statement changes were required.

Background & Definitions

BRAF and MEK inhibitors act on the MAPK pathway by inhibiting signaling driven by activating BRAF mutations (most commonly V600E and V600K), which constitutively activate the MAPK-ERK cascade and promote tumor growth.

Policy purpose: To summarize when individual BRAF and MEK agents, and specific combinations, are considered medically necessary across tumor types (including melanoma, metastatic colorectal cancer, NSCLC, ovarian cancer, anaplastic thyroid cancer, histiocytic neoplasms, NF1, and pediatric low-grade glioma) and across age groups (adult and pediatric indications), based on mutation status, prior therapies, and other agent-specific criteria.

Term	Definition
BRAF V600 mutation	Activating mutations at codon 600 of BRAF (primarily V600E or V600K) that drive MAPK pathway signaling and predict response to BRAF/MEK inhibitors.

Revision History

2026-03-01review_noteLatest

Reviewed prescribing information for all drugs in the policy and reviewed NCCN guideline; Evidence Review updated to reflect American Cancer Society 2026 statistics; no clinical policy statement changes for 03/01/26 update.

2026-02-23material_change

OpenPayer

BRAF and MEK Inhibitors

Coverage Summary & Scope

Combination therapy for melanoma (medically necessary)

Combination therapy for metastatic colorectal cancer (medically necessary)

Combination therapy for metastatic NSCLC (medically necessary)

Combination therapy for ovarian cancer (medically necessary)

Tafinlar + Mekinist: Other combination indications (medically necessary)

Monotherapy indications (medically necessary)

Neurofibromatosis type 1 therapies (medically necessary)

Pediatric low-grade glioma (medically necessary)

Not Medically Necessary & Investigational / Unproven

Provider Actions & Prior Authorization

Applicable Codes

Clinical Evidence Summary

Background & Definitions

Revision History