Health Net encorafenib (Braftovi) Coverage Update

Coverage Criteria for Encorafenib (Braftovi)

inv-01: Initial Approval — Melanoma

Covered when ALL of the following are met

Melanoma initial criteria: 1) Diagnosis of melanoma with BRAF V600E or V600K mutation; 2) Disease is unresectable or metastatic OR Stage III as adjuvant therapy OR limited resectable melanoma; 3) Prescribed by or in consultation with an oncologist; 4) Age >= 18 years; 5) For unresectable/metastatic melanoma: prescribed in combination with binimetinib (Mektovi) unless combination therapy is contraindicated; 6) For adjuvant or limited resectable melanoma: prescribed in combination with binimetinib and member has unacceptable toxicities to Tafinlar/Mekinist or those agents are not appropriate; 7) Member must use generic encorafenib if available unless contraindicated or clinically significant adverse effects are experienced; 8) Dose does not exceed 450 mg/day and 6 capsules per day, or the dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).

Prescribed regimen must be FDA-approved or recommended by NCCN.

inv-02: Initial Approval — Colon/Rectal Cancer (mCRC)

Covered when ALL of the following are met

mCRC initial criteria: 1) Diagnosis of colon or rectal cancer with BRAF V600E mutation; 2) Disease is unresectable, advanced, or metastatic; 3) Prescribed by or in consultation with an oncologist; 4) Age > 18 years; 5) Prescribed in combination with either cetuximab (Erbitux) or panitumumab (Vectibix) and either: a) in combination with mFOLFOX6 (labeled), or b) as subsequent therapy following prior oxaliplatin- or irinotecan-based therapy (or prior adjuvant therapy within the past 12 months); 6) Member must use generic encorafenib if available unless contraindicated or clinically significant adverse effects are experienced; 7) Dose does not exceed 300 mg/day and 4 capsules per day, or the dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).

Prior authorization may be required for Erbitux or Vectibix; Vectibix combination noted as off-label per NCCN guidance in policy history.

inv-03: Initial Approval — Non-Small Cell Lung Cancer (NSCLC)

Covered when ALL of the following are met

NSCLC initial criteria: 1) Diagnosis of advanced, metastatic, or recurrent non-small cell lung cancer with BRAF V600E mutation; 2) Prescribed by or in consultation with an oncologist; 3) Age >= 18 years; 4) Prescribed in combination with binimetinib (Mektovi); 5) Member must use generic encorafenib if available unless contraindicated or clinically significant adverse effects are experienced; 6) Dose does not exceed 450 mg/day and 6 capsules per day, or the dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).

Prescribed regimen must be FDA-approved or recommended by NCCN.

inv-04: Continued Therapy

Covered when ALL of the following are met

Continued therapy criteria: 1) Member is currently receiving Braftovi via the benefit, or documentation supports current receipt of encorafenib for a covered indication and has received therapy for at least 30 days; 2) Member is responding positively to therapy; 3) If request is for a dose increase, the new dose must meet indication-specific maximums (melanoma/NSCLC: <=450 mg/day and <=6 capsules/day; colon/rectal cancer: <=300 mg/day and <=4 capsules/day) or be supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence); 4) Member must use generic encorafenib if available unless contraindicated or clinically significant adverse effects are experienced.

Approval durations: Medicaid/HIM 12 months; Commercial 12 months or duration of request, whichever is less.

inv-05: Indication-specific dosing and combination use

Covered when used per FDA or NCCN-supported indication and dosing as specified below

Melanoma/NSCLC dosing: Encorafenib 450 mg PO once daily in combination with binimetinib (Mektovi) until disease progression or unacceptable toxicity.450 mg/day

NCCN allows Braftovi monotherapy in melanoma if Mektovi is contraindicated (category 2A).

Colon/Rectal cancer dosing: Encorafenib 300 mg PO once daily in combination with cetuximab (Erbitux) plus mFOLFOX6 (labeled) or with panitumumab (Vectibix) as an off-label option per NCCN.300 mg/day

FDA approval added for combination with cetuximab and mFOLFOX6; combination with Vectibix is off-label per NCCN guidance noted in policy history.

Encorafenib (Braftovi) is approved for specific BRAF V600E or V600K mutated malignancies only when used in the FDA‑labeled combinations or as specified by the policy. The agent is not indicated for tumors with wild‑type BRAF (melanoma, colorectal cancer, or NSCLC). Prior authorization is required and coverage is contingent on documentation of the diagnosis, mutation status by an FDA‑approved test, prescriber specialty, age, and use in the approved combination and dosing limits described in the criteria.

Per the 2Q 2024 annual review and NCCN compendium update, appendiceal adenocarcinoma was removed from the colorectal cancer indication for encorafenib and is no longer considered a supported indication for coverage under this policy.

Non‑FDA approved (off‑label) indications that are not specifically addressed in this policy are not authorized unless the provider submits sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies (commercial, marketplace, or Medicaid) referenced in the policy.

Use of encorafenib for appendiceal adenocarcinoma is not supported for coverage following its removal from the NCCN compendium (2Q 2024); requests for this diagnosis are expected to be denied absent compelling, guideline‑supported evidence.

Dosing, Strengths, and Key Numeric Limits

inv-10: Maximum daily dose (melanoma/NSCLC)

Maximum daily dose450 mg/day (Melanoma and NSCLC)

Capsule equivalentUp to 6 capsules per day (75 mg capsules) = 450 mg/day

ContextDose applies when encorafenib is used in combination with binimetinib (Mektovi) for unresectable/metastatic melanoma or NSCLC or per NCCN/FDA-supported regimens

inv-11: Maximum daily dose (colon/rectal cancer)

Maximum daily dose300 mg/day (Colon/Rectal cancer)

Capsule equivalentUp to 4 capsules per day (75 mg capsules) = 300 mg/day

Context

Initial Therapy Authorization Criteria

inv-24: Initial therapy — initial authorization criteria vary by diagnosis and must be met for coverage

Initial authorization criteria vary by diagnosis and must be met for coverage

Initial therapy per indication: See the Initial Approval criteria for each indication: melanoma (BRAF V600E/V600K; combination with binimetinib unless contraindicated; age >=18; dose limits 450 mg/day/6 capsules), colon/rectal cancer (BRAF V600E; combination with cetuximab ± mFOLFOX6 or Vectibix as specified; age >18; dose limits 300 mg/day/4 capsules), and NSCLC (BRAF V600E; combination with binimetinib; age >=18; dose limits 450 mg/day/6 capsules).

Prescriber specialty, mutation status, age, combination agent, generic use, and indication-specific dose limits are required as specified in each initial approval section. Prior authorization may be required for combination agents (Mektovi, Erbitux, Vectibix).

inv-25: Initial therapy dosing — initial dosing by indication

Initial dosing by indication

Melanoma/NSCLC initial therapy: 450 mg PO once daily in combination with Mektovi until disease progression or unacceptable toxicity.

Criteria to Continue Therapy and Approval Durations

inv-26: Continuation therapy — criteria required to continue therapy

Criteria required to continue therapy

Continuation nodes: 1) Member currently receiving Braftovi for a covered indication for at least 30 days or documentation supports current receipt; 2) Member is responding positively to therapy; 3) Dose increases must meet indication-specific limits (melanoma/NSCLC: <=450 mg/day and <=6 capsules/day; colon/rectal: <=300 mg/day and <=4 capsules/day) or be supported by practice guidelines/peer-reviewed literature (prescriber must submit supporting evidence); 4) Use of generic encorafenib is required if available unless contraindicated or clinically significant adverse effects are experienced.

inv-27: Continuation/approval duration — approval durations and continuation considerations

Approval durations and continuation considerations

Duration: Commercial approval durations: 12 months or duration of request, whichever is less; Medicaid/HIM: 12 months for continued therapy as specified in the policy approval section.12 months

Provider Requirements and Documentation

Prior Authorization

Prior Authorization Required — Documentation and Indication Risk

Prior authorization required. Provider must submit documentation (office chart notes, laboratory results, pathology or mutation testing reports, and any other relevant clinical information) demonstrating the member meets all applicable approval criteria, including diagnosis, BRAF V600E or V600K mutation status where required, treating oncologist involvement, age, and details of combination regimens or contraindications.

Affected lines of business may require prior authorization
Oncologist prescribing or consultation must be documented
Mutation testing report (BRAF V600E or V600K) should be included when applicable

Documentation Required

Required Documentation

Provider must submit supporting documentation at the time of request. Acceptable documentation includes office chart notes, pathology/molecular testing reports confirming mutation status, prior therapy records, medication history, relevant laboratory results, and rationale for use when prescribing off-label regimens. Insufficient or missing documentation may result in denial.

Step Therapy and Sequencing Considerations

Clinical Setting	Step therapy / prior treatment requirement	Notes
Adjuvant or limited resectable melanoma (Stage III)	Prior intolerance to or unacceptable toxicities from alternative BRAF/MEK agents (eg, dabrafenib/trametinib [Tafinlar/Mekinist]) may be required before Braftovi is used as adjuvant/limited resectable therapy	Policy specifies combination with binimetinib (Mektovi) for most melanoma indications; for adjuvant/limited resectable disease prior toxicity or inappropriateness of Tafinlar/Mekinist is an explicit criterion
Unresectable or metastatic melanoma	No routine step requiring prior BRAF/MEK agents for unresectable/metastatic disease when prescribed in combination with binimetinib; if used as monotherapy it must be supported by NCCN or guidelines (eg, Mektovi contraindicated)	Dose limits: ≤450 mg/day and ≤6 capsules/day; generic encorafenib preferred if available
Metastatic colorectal cancer (mCRC) with BRAF V600E mutation	May require prior oxaliplatin- or irinotecan-based chemotherapy when used as subsequent therapy; alternatively covered in combination with cetuximab + mFOLFOX6 (labeled) without prior therapy requirement	Policy allows encorafenib with cetuximab + mFOLFOX6 (labeled) or with panitumumab (Vectibix) as subsequent therapy; dose limits: ≤300 mg/day and ≤4 capsules/day; prior authorization may be required for cetuximab/Vectibix

Topic	Historical note
Template and sequencing updates	Multiple annual reviews applied template changes and therapy sequencing updates (noting revisions in 2Q 2021, 2Q 2022, and 2Q 2023); these updates adjusted wording and approval-duration conventions across indications but do not by themselves define specific new step requirements
Approval duration standardization	Commercial approval durations were revised to 12 months during the 2Q 2022 annual review; this is a historical administrative change reflected in the policy history
Specific step therapy details absent in history	Policy history entries describe template and indication additions/removals but do not list additional explicit step therapy requirements beyond those present in the clinical criteria sections

Dispensing Quantity Limits and Capsule Strengths

inv-30: Encorafenib (Braftovi) — capsules per day limits tied to mg/day limits

Quantity ruleCapsules-per-day limits are tied to mg/day limits for encorafenib (Braftovi)

Melanoma/NSCLC limitMaximum 6 capsules/day when dosing is 450 mg/day

Colon/Rectal limitMaximum 4 capsules/day when dosing is 300 mg/day

inv-31: Encorafenib — capsule strengths available inform dispensing; dosing determines quantity

Available strength75 mg capsules

Dispensing noteQuantity dispensed should reflect prescribed daily dose (e.g., 4 capsules/day for 300 mg, 6 capsules/day for 450 mg)

Background on Encorafenib

Encorafenib is an oral kinase inhibitor that targets BRAF V600 mutations. It is indicated in combination regimens: with binimetinib (Mektovi) for unresectable or metastatic melanoma harboring BRAF V600E or V600K mutations and for metastatic NSCLC with BRAF V600E mutation, and with cetuximab (± mFOLFOX6) for metastatic colorectal cancer with BRAF V600E mutation. Dosing and combination requirements in the policy reflect the FDA‑approved regimens and companion diagnostic testing requirements.

Key Definitions and Abbreviations

inv-21: BRAF — B-Raf proto-oncogene, serine/threonine kinase

TermBRAF — B-Raf proto-oncogene, serine/threonine kinase

RelevanceMutation (e.g., V600E/V600K) status is required for encorafenib coverage

AcronymBRAF in appendices defined as B-Raf proto-oncogene, serine/threonine kinase

inv-31: CRC / mCRC — Colorectal cancer / metastatic colorectal cancer

DefinitionCRC / mCRC — Colorectal cancer / metastatic colorectal cancer

Coverage noteEncorafenib coverage for mCRC requires BRAF V600E mutation and combination therapy as specified (e.g., cetuximab + mFOLFOX6 or Vectibix per NCCN)

Policy Revision History

2025-02-13annual_reviewLatest

2Q 2025 annual review: clarified that combination use of encorafenib with panitumumab (Vectibix) for colorectal cancer is off-label per NCCN and references were reviewed and updated.

2025-01-02added

RT4: added newly FDA‑approved use in metastatic colorectal cancer in combination with cetuximab and mFOLFOX6.

2024-02-07removed

OpenPayer

Encorafenib (Braftovi) coverage

Coverage Criteria for Encorafenib (Braftovi)

Dosing, Strengths, and Key Numeric Limits

Initial Therapy Authorization Criteria

Criteria to Continue Therapy and Approval Durations

Provider Requirements and Documentation

Step Therapy and Sequencing Considerations

Dispensing Quantity Limits and Capsule Strengths

Background on Encorafenib

Key Definitions and Abbreviations

Policy Revision History