CurrentCentenePolicy CP PHAR.127

Encorafenib (Braftovi)

Defines medical necessity criteria, approval durations, and continuation requirements for encorafenib (Braftovi) across melanoma, metastatic colorectal/rectal cancer, and non-small cell lung cancer for Centene lines of business (Commercial, HIM, Medicaid). Also includes dosing limits, generic redirection, and off-label guidance referral.

Policy Summary

PayerCentene

PolicyEncorafenib (Braftovi)

Policy CodePolicy CP PHAR.127

Change TypeMultiple annual reviews and FDA indication additions

Effective DateSep 1, 2018

Next Review Date

Key ActionProvider must submit documentation (office notes, labs, other clinical information) supporting that member meets all approval criteria.

POLICY UPDATE CHANGES

Added newly FDA-approved and NCCN-supported use in NSCLC in combination with Mektovi (11.02.23).

Added newly FDA-approved use in mCRC in combination with cetuximab and mFOLFOX6 (01.02.25).

2Q 2025 annual review clarified combination use with Vectibix is off-label per NCCN and updated references (02.13.25; P&T 05.25).

2Q 2024 annual review removed appendiceal adenocarcinoma and redundant criteria; references updated (02.07.24; P&T 05.24).

3FDA-approved disease indications covered

12Commercial approval duration options (months)

30Minimum days on therapy for continuation

Scope: Defines medical necessity criteria, approval durations, and continuation requirements for encorafenib (Braftovi) across melanoma, metastatic colorectal/rectal cancer, and non-small cell lung cancer for Centene lines of business (Commercial, HIM, Medicaid). Policy applies Centene-wide with line-of-business specific approval durations: Commercial: 12 months or duration of request, whichever is less; Medicaid/HIM: 6 months.

Coverage stance: covered_with_criteria. Policy number: CP PHAR.127. FDA-approved indications covered per prescribing information include: melanoma (BRAF V600E or V600K, with binimetinib), metastatic colorectal cancer (mCRC) with BRAF V600E (with cetuximab and/or cetuximab+mFOLFOX6), and non-small cell lung cancer (NSCLC) with BRAF V600E, in combination with binimetinib).

Effective date: 09.01.18. Last review date / P&T: 05.25.

Initial Approval Criteria — Melanoma

Initial Approval Criteria - Melanoma

Covered when ALL of the following are met:

ALL of the following

Diagnosis of melanoma with BRAF V600E or V600K mutation
Detected by an FDA-approved test
Disease setting (one of)
- Unresectable or metastatic melanoma
- Stage III melanoma as adjuvant therapy
- Limited resectable melanoma
Prescribed by or in consultation with an oncologist
Age ≥ 18 years
Combination & toxicity rules (melanoma-specific)
- For unresectable or metastatic melanoma: prescribed in combination with binimetinib (Mektovi), unless Braftovi/Mektovi combination therapy is contraindicated
- For adjuvant therapy or limited resectable melanoma: prescribed in combination with binimetinib
- For adjuvant therapy or limited resectable melanoma: member has unacceptable toxicities to the Tafinlar/Mekinist regimen or Tafinlar/Mekinist are not appropriate on the basis of side-effect profiles
Dose requirement (one of)
- Dose does not exceed 450 mg per day and does not exceed 6 capsules per day450 mg per day; 6 capsules per day
- Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

Initial Approval Criteria — Colon & Rectal Cancer (mCRC)

Initial Approval Criteria - Colon/Rectal Cancer (including appendiceal when applicable)

Covered when ALL of the following are met:

ALL of the following

Diagnosis of colon cancer or rectal cancer with BRAF V600E mutation
Detected by an FDA-approved test
Disease is unresectable, advanced, or metastatic
Prescribed by or in consultation with an oncologist
Age > 18 years
Combination requirements (one of)
- Prescribed in combination with either cetuximab (Erbitux) or panitumumab (Vectibix)
  Vectibix is off-label per NCCN
- Prescribed in combination with cetuximab and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin)
Prior therapy / setting (one of)
- Request is for subsequent therapy following previous treatment (e.g., oxaliplatin- or irinotecan-based therapy, Opdivo/Keytruda, FOLFOX, CapeOX)
- Member previously received adjuvant therapy (e.g., FOLFOX, CapeOX) within the past 12 months
Dose requirement (one of)
- Dose does not exceed 300 mg per day and does not exceed 4 capsules per day300 mg per day; 4 capsules per day
- Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

Initial Approval Criteria — Non‑Small Cell Lung Cancer (NSCLC)

Initial Approval Criteria - Non-Small Cell Lung Cancer (NSCLC)

Covered when ALL of the following are met:

ALL of the following

Diagnosis of advanced, metastatic, or recurrent NSCLC with BRAF V600E mutation positive
Detected by an FDA-approved test
Prescribed by or in consultation with an oncologist
Age ≥ 18 years
Prescribed in combination with binimetinib (Mektovi)
Dose requirement (one of)
- Dose does not exceed 450 mg per day and does not exceed 6 capsules per day450 mg per day; 6 capsules per day
- Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

Continuation / Reauthorization Criteria (All Indications)

Continued Therapy (All indications)

Covered when ALL of the following are met:

ALL of the following

Member is currently receiving medication via Centene benefit, or documentation supports current receipt of Braftovi for a covered indication and has received medication for at least 30 days
Member is responding positively to therapy (clinical documentation required)
Dose increase rules (if request for dose increase)
- Melanoma: new dose does not exceed 450 mg per day and 6 capsules per day450 mg per day; 6 capsules per day
- Colon/rectal cancer: new dose does not exceed 300 mg per day and 4 capsules per day300 mg per day; 4 capsules per day
- NSCLC: new dose does not exceed 450 mg per day and 6 capsules per day450 mg per day; 6 capsules per day
- New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)
Member must use generic encorafenib, if available, unless contraindicated or clinically significant adverse effects are experienced

Other Diagnoses / Off‑Label Guidance

Other Diagnoses / Off-Label

Covered only when meeting formulary/no-coverage or off-label policies:

ANY of the following

If drug is on the formulary/PDL, follow the no coverage criteria policy for the relevant line of business: CP.CPA.190 (commercial), HIM.PA.33 (marketplace), CP.PMN.255 (Medicaid)
If drug NOT on formulary/PDL, follow the non-formulary policy: CP.CPA.190 (commercial), HIM.PA.103 (marketplace), CP.PMN.16 (Medicaid)
If requested use is not specifically listed and criterion for covered indications does not apply, refer to off-label use policy: CP.CPA.09 (commercial), HIM.PA.154 (marketplace), CP.PMN.53 (Medicaid)

Diagnoses/Indications Not Authorized

Coverage not authorized when:

Non–FDA approved indications that are not addressed in this policy, unless sufficient documentation of efficacy and safety is provided per off-label use policies

Refer to off-label use policies: CP.CPA.09 (commercial), HIM.PA.154 (marketplace), CP.PMN.53 (Medicaid)

Provider Actions & Authorization Requirements

Documentation Required

Submit clinical documentation

Submit clinical documentation such as office chart notes, laboratory results, or other clinical information supporting that the member has met all approval criteria.

Prior Authorization

Prior authorization required

Prior authorization may be required for encorafenib (Braftovi) and for combination agents referenced in the criteria (for example, binimetinib/Mektovi, cetuximab/Erbitux, panitumumab/Vectibix). Prescriptions should be reviewed for PA requirements prior to dispensing.

Prior authorization may be required for Mektovi
Prior authorization may be required for Erbitux and Vectibix

Documentation Required

Mutation testing requirement

Mutation testing for a qualifying BRAF V600E or V600K mutation must be performed and documented. Approval for indications requires BRAF V600E or V600K mutation positive status as detected by an FDA‑approved test.

BRAF V600E or V600K mutation must be documented
Mutation detection must be by an FDA‑approved test

Billing Rule

Generic redirection

Members must use generic encorafenib when available unless contraindicated or clinically significant adverse effects occur. Dose limits: melanoma and NSCLC—up to 450 mg/day (6 capsules/day); colorectal cancer—up to 300 mg/day (4 capsules/day).

Use generic encorafenib if available unless contraindicated
Melanoma/NSCLC dose limit: 450 mg/day; 6 capsules/day
Colon/rectal cancer dose limit: 300 mg/day; 4 capsules/day

Denial Risk

Not authorized for non‑FDA indications without evidence

Requests for non‑FDA approved indications not addressed by this policy are not authorized unless sufficient documentation of efficacy and safety is submitted per the applicable off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) or other evidence of coverage documents.

Non‑FDA indications require supporting evidence per off‑label policies: CP.CPA.09 (commercial), HIM.PA.154 (marketplace), CP.PMN.53 (Medicaid)

References & Evidence

Key evidence and references include the Braftovi Prescribing Information (Dec 2024) and the NCCN Drugs and Biologics Compendium and related 2025 NCCN disease guidelines (references updated February 13, 2025).

Background notes from the policy reference FDA approvals for labeled combination regimens (e.g., with binimetinib for melanoma and NSCLC; with cetuximab and with cetuximab+mFOLFOX6 for mCRC) and indicate that NCCN compendium recommendations and recent label changes (including incorporation of NSCLC and the mCRC mFOLFOX6 combination) informed the policy.

The policy history documents NCCN-related clarifications, including that combination use with panitumumab (Vectibix) is considered off-label per NCCN updates and that recent label and compendium changes were incorporated into the policy.

Background & Definitions

Background: Encorafenib (Braftovi) is a kinase inhibitor FDA-approved in combination regimens for BRAF V600E or V600K mutant melanoma, metastatic colorectal cancer, and non-small cell lung cancer. The policy applies Centene-wide (Commercial, HIM, Medicaid) and references NCCN and the prescribing information when defining medically necessary uses and combination regimens.

Policy application: Coverage criteria require oncologist involvement, mutation detection by an FDA-approved test for labeled indications, adherence to combination/dosing rules per indication, and generic redirection where applicable. Line-of-business specific approval durations are applied as noted in the policy.

Definitions: BRAF — B-Raf proto-oncogene, serine/threonine kinase.

mCRC — metastatic colorectal cancer.

Policy Revision History

11.02.23added

Added newly FDA-approved and NCCN-supported use in non-small cell lung cancer (NSCLC) in combination with Mektovi (binimetinib).

02.07.24revised

2Q 2024 annual review removed appendiceal adenocarcinoma and redundant criteria; references updated (P&T 05.24).

01.02.25added

Added newly FDA-approved use in metastatic colorectal cancer (mCRC) in combination with cetuximab and mFOLFOX6.

02.13.25revisedLatest

2Q 2025 annual review clarified combination use with Vectibix (panitumumab) is off-label per NCCN and updated references (P&T 05.25).

OpenPayer

Encorafenib (Braftovi)

Coverage Summary & Scope

Initial Approval Criteria — Melanoma

Initial Approval Criteria — Colon & Rectal Cancer (mCRC)

Initial Approval Criteria — Non‑Small Cell Lung Cancer (NSCLC)

Continuation / Reauthorization Criteria (All Indications)

Other Diagnoses / Off‑Label Guidance

Applicable Codes & Formulation

Provider Actions & Authorization Requirements

References & Evidence

Background & Definitions

Policy Revision History