mhn Cobimetinib (Cotellic) Coverage Update

Coverage Criteria

Initial Therapy - Melanoma

Covered when ALL of the following are met for melanoma:

Melanoma initial therapy: 1. Diagnosis of melanoma with BRAF V600E or V600K mutation; 2. Disease is one of: unresectable or metastatic melanoma; stage III melanoma as adjuvant or neoadjuvant therapy; or limited resectable melanoma; 3. Prescribed by or in consultation with an oncologist; 4. Age ≥ 18 years; 5. Prescribed in combination with vemurafenib (Zelboraf) (prior authorization for Zelboraf may be required); 6. For stage III or limited resectable melanoma, member has unacceptable toxicities to Tafinlar/Mekinist or those agents are not appropriate based on side-effect profiles; 7. Member must use cobimetinib, if available, unless contraindicated or clinically significant adverse effects are experienced; 8. Request meets one of the following: (a) dose does not exceed both i. 60 mg per day and ii. 3 tablets per day for the first 21 days of each 28-day cycle; or (b) dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).dose limits: 60 mg/day; 3 tablets/day; schedule: 21 days on/7 days off

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

Initial Therapy - Histiocytic Neoplasms

Covered when ALL of the following are met for histiocytic neoplasms:

Histiocytic neoplasms initial therapy: 1. Diagnosis of a histiocytic neoplasm (examples: Langerhans cell histiocytosis [LCH], Rosai‑Dorfman disease, Erdheim‑Chester disease [ECD], xanthogranuloma, mixed histiocytosis); 2. Prescribed by or in consultation with an oncologist or hematologist; 3. Age ≥ 18 years; 4. Prescribed as a single agent; 5. Disease is multi‑system, recurrent/refractory, or single‑system unlikely to benefit from conventional therapies; 6. If disease is BRAF‑mutated, member has either (a) documented BRAF V600E and is unable to access a BRAF inhibitor or prior BRAF inhibitor was discontinued due to intolerable side effects/toxicity, or (b) BRAF‑mutated ECD or LCH with disease progression on BRAF inhibitor therapy; 7. Member must use cobimetinib, if available, unless contraindicated or clinically significant adverse effects are experienced; 8. Request meets one of the following: (a) dose does not exceed both i. 60 mg per day and ii. 3 tablets per day for the first 21 days of each 28‑day cycle; or (b) dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).dose limits: 60 mg/day; 3 tablets/day; schedule: 21 days on/7 days off

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

Initial Therapy - Central Nervous System Cancers (off-label)

Covered when ALL of the following are met for select CNS cancers (off-label):

CNS cancers initial therapy: 1. Diagnosis of one of the following: pilocytic astrocytoma; circumscribed ganglioglioma/neuroglioma/glioneuronal tumor; pleomorphic xanthoastrocytoma (WHO grade 2); recurrent or progressive circumscribed glioma; recurrent or progressive glioblastoma; recurrent or progressive high‑grade glioma; or brain metastases; 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Disease positive for BRAF V600E mutation; 5. Prescribed in combination with vemurafenib (Zelboraf) (prior authorization for Zelboraf may be required); 6. Member must use cobimetinib, if available, unless contraindicated or clinically significant adverse effects are experienced; 7. Request meets one of the following: (a) dose does not exceed both i. 60 mg per day and ii. 3 tablets per day for the first 21 days of each 28‑day cycle; or (b) dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).dose limits: 60 mg/day; 3 tablets/day; schedule: 21 days on/7 days off

Prescribed regimen must be FDA‑approved or recommended by NCCN. Policy updates (2Q2024–2Q2025) expanded CNS tumor types per NCCN 2A recommendations.

Continuation Therapy

Covered when ALL of the following are met for continuation/renewal:

Continuation therapy: 1. Member is currently receiving cobimetinib via the Centene benefit, or documentation supports that the member has received cobimetinib for a covered indication for at least 30 days; 2. Member is responding positively to therapy; 3. Member must use cobimetinib, if available, unless contraindicated or clinically significant adverse effects are experienced; 4. Request meets one of the following: (a) dose does not exceed both i. 60 mg per day and ii. 3 tablets per day for the first 21 days of each 28‑day cycle; or (b) 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.

Other diagnoses/indications

Other/off-label uses:

Other/Off-label: 1. If cobimetinib has undergone a label change within the last 6 months that is not yet reflected in this policy, refer to the applicable no‑coverage or non‑formulary policy for the member's line of business (e.g., CP.CPA.190, HIM.PA.33, CP.PMN.255 for formulary; CP.CPA.190, HIM.PA.103, CP.PMN.16 for non‑formulary). 2. If the requested use (diagnosis, age, dosing) is not listed under the policy's exclusions AND criterion 1 does not apply, refer to the off‑label use policy for the applicable line of business (CP.CPA.09 commercial; HIM.PA.154 marketplace; CP.PMN.53 Medicaid).

Prescribers must submit supporting evidence when dose/regimen is supported by guidelines or literature.

Covered Oncology Indications (summary)

Covered when meeting NCCN-supported or FDA-labeled indications as specified below

Melanoma indications: Includes unresectable or metastatic melanoma; stage III and limited resectable melanoma considerations per NCCN. Note: 2Q2025 revision removed a separate re‑induction criterion because re‑induction is covered under unresectable/metastatic melanoma.

References NCCN updates and prior requirement for trial of Tafinlar/Mekinist for certain settings.

Histiocytic neoplasms: Policy revised to allow a broad range of histiocytic neoplasm types per the prescribing information (FDA PI), aligning coverage with FDA‑approved indication for single‑agent use in appropriate histiocytic neoplasms.

Added/updated per prescribing information and NCCN where applicable.

Central nervous system cancers: Includes selected CNS tumors per NCCN 2A recommendations and 2Q2024–2Q2025 updates: WHO grade 2–4 adult IDH‑mutant astrocytoma, WHO grade 2–3 oligodendroglioma, pilocytic astrocytoma, circumscribed ganglioglioma/neuroglioma/glioneuronal tumor, pleomorphic xanthoastrocytoma, recurrent/progressive circumscribed glioma, recurrent/progressive glioblastoma, recurrent/progressive high‑grade glioma, and brain metastases.

Non‑FDA approved 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: CP.CPA.09 (commercial), HIM.PA.154 (health insurance marketplace), or CP.PMN.53 (Medicaid), or unless such use is otherwise supported by the member’s evidence of coverage documents.

Policy terminology related to central nervous system tumors was updated to align with the NCCN compendium; specifically, references to “anaplastic glioma” and “grade 2 glioma” were removed because these terms are no longer used in the NCCN listing.

Treatment of melanoma in patients whose tumor is BRAF wild‑type is not medically necessary and is explicitly excluded from coverage under this policy.

This clinical policy is intended as a guide to medical necessity to assist coverage determinations but does not guarantee payment. Coverage and benefit administration remain subject to the member’s specific plan terms, conditions, exclusions, limitations, and applicable state or federal requirements.

Covered Regimens and Dosing

Indication	Regimen / Dosing	Dose limit
Melanoma (in combination with vemurafenib)
Cobimetinib 60 mg PO once daily for 21 days followed by 7 days off in a 28-day cycle; given in combination with vemurafenib (Zelboraf).
Dose does not exceed 60 mg/day (three 20 mg tablets) for the first 21 days of each 28-day cycle.

Indication	Regimen / Dosing	Dose limit
Histiocytic neoplasms (single-agent use)
Cobimetinib 60 mg PO once daily for 21 days followed by 7 days off in a 28-day cycle as single-agent therapy.
Dose does not exceed 60 mg/day (three 20 mg tablets) for the first 21 days of each 28-day cycle.

Indication	Regimen / Dosing	Biomarker requirement
Select central nervous system cancers (in combination with vemurafenib)
Cobimetinib dosed per melanoma regimen: 60 mg PO once daily for 21 days followed by 7 days off in a 28-day cycle, used in combination with vemurafenib (Zelboraf).
Requires documented BRAF V600E mutation in the tumor.

Indication	Regimen / Guidance	Coverage stance
Melanoma where combination MEK + BRAF inhibitor regimens are appropriate
Cobimetinib in combination with BRAF inhibitors per prescribing information and NCCN compendia; dosing and use should follow PI and relevant NCCN recommendations.
Covered when used per PI and NCCN-supported indications and criteria.

Coding and Approval Durations

Codes referenced (unspecified in this section)mixed

affected codes

Document references changes to approval durations and templates; specific CPT/HCPCS/ICD codes not listed in this document portion.

Dosing schedule — cobimetinib

Dosing schedule60 mg PO once daily for 21 days followed by 7 days off (28-day cycle)

Maximum daily dose60 mg per day (three 20 mg tablets)

Cycle length28-day cycle (21 days on, 7 days off)

Dose support for off-label useDose supported by practice guidelines or peer-reviewed literature if exceeding limits (prescriber must submit evidence)

Approval duration

Standard approval duration (commercial)12 months or duration of request, whichever is less

Typical Medicaid/HIM approval durations (context)

Provider Actions and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for requests for Cotellic (cobimetinib). Providers must document that the member meets the applicable, criteria-based indications in the policy (e.g., BRAF V600E or V600K mutation for melanoma; BRAF V600E for CNS and other specified indications) and that the prescribed regimen is FDA‑approved or recommended by NCCN when applicable. Prior authorization may also be required for concomitant vemurafenib (Zelboraf®).

Prior authorization required for Cotellic (cobimetinib).
Prior authorization may be required for concomitant Zelboraf® (vemurafenib).

Prior Authorization

Prior Authorization and Approval Duration

Approval durations and prior authorization expectations have been updated over time. Commercial approval durations have been revised to 12 months or the duration of the request, whichever is less, for covered indications unless otherwise specified. Oncology orders are subject to prior authorization and will be reviewed against the current policy criteria and applicable NCCN-supported indications.

Commercial approval durations: 12 months or duration of request, whichever is less, unless otherwise stated.

Line of Therapy

first-line | continuation

Line of therapy: Policy addresses initial therapy and continuation for adults (age ≥ 18 years); specific prior‑line requirements exist for histiocytic neoplasms regarding prior BRAF inhibitor therapy or access. No explicit ECOG performance status requirement is specified in these sections.

first-line | second-line

Line of therapy notes: Policy updates reference use in adjuvant/neoadjuvant settings for stage III melanoma and adjustments to re‑induction language (2Q2024–2Q2025); explicit first‑line vs second‑line designations and other line‑of‑therapy details are contained elsewhere in the full policy.

Biomarker Requirements

BRAF V600E or V600K — biomarker requirement

Required biomarker for melanoma and select CNS cancersBRAF V600E or V600K mutation required for melanoma; BRAF V600E required for listed CNS tumors

Use with BRAF inhibitorCobimetinib prescribed in combination with vemurafenib (Zelboraf) for melanoma and CNS indications where specified

Age requirementCoverage applies to adults: Age ≥ 18 years

BRAF mutation (general) — histiocytic neoplasms

Required biomarker for histiocytic neoplasms (when specified)Presence of a BRAF mutation (e.g., V600E) is considered in criteria for histiocytic neoplasms

Access/prior therapy conditionsIf BRAF‑mutated, member must be unable to access a BRAF inhibitor or have discontinued/failed prior BRAF inhibitor therapy

Definitions and Abbreviations

BRAF — definition

Gene/protein nameB-Raf proto-oncogene serine/threonine kinase

AbbreviationBRAF

Reference locationDefined in Appendix A: Abbreviation/Acronym Key

Histiocytic neoplasms — abbreviations and examples

LCHLangerhans cell histiocytosis

ECDErdheim-Chester disease

Other examplesAlso includes Rosai-Dorfman disease, xanthogranuloma, mixed histiocytosis as listed in policy

Background

Cobimetinib (Cotellic) is a MEK kinase inhibitor used in combination with vemurafenib for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations and is also described in the policy for single‑agent use in histiocytic neoplasms and select NCCN‑supported central nervous system tumor indications.

OpenPayer

Cobimetinib (Cotellic) coverage

Coverage Criteria

Covered Regimens and Dosing

Coding and Approval Durations

Provider Actions and Documentation

Line of Therapy

Biomarker Requirements

Definitions and Abbreviations

Background