ModifiedCentenePolicy CP PHAR.380

Cobimetinib (Cotellic) coverage

Defines medical necessity criteria, dosing, and authorization rules for cobimetinib (Cotellic) for commercial, HIM, and Medicaid lines of business within Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyCobimetinib (Cotellic) coverage

Policy CodePolicy CP PHAR.380

Change TypeCriteria added/modified to align with FDA label and NCCN (material)

Effective DateNov 16, 2016

Next Review DateN/A

Key ActionPrior authorization required; provider must document diagnosis, BRAF V600E or V600K mutation status, oncologist involvement, and prescribed regimen.

SourceLink

POLICY UPDATE CHANGES

For CNS cancers, criteria were updated to include WHO grade 2 or 3 adult oligodendroglioma and WHO 2,3, or 4 adult IDH‑mutant astrocytoma per NCCN-supported 2A recommendation.

Melanoma criteria revised to add stage III melanoma as adjuvant therapy, limited resectable melanoma, requirements for trial of Tafinlar/Mekinist, and later removed re‑induction therapy criterion for melanoma per NCCN.

Histiocytic neoplasms criteria converted from off‑label to FDA‑approved use and revised to allow a broad range of histiocytic neoplasm types per product information.

Central nervous system (CNS) cancer indications expanded to include additional circumscribed tumors (pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, circumscribed ganglioglioma/neuroglioma/glioneuronal tumor) and recurrent/progressive high‑grade glioma and brain metastases per NCCN.

20 mgTablet strength

60 mg/dayMax dose (21/28 days)

12 mo

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6 moMedicaid/HIM approval

2Q reviewsP&T review activity

Coverage Criteria

Initial Therapy - Melanoma

Initial Approval Criteria for melanoma (must meet ALL):

ALL of the following

Diagnosis of melanoma with BRAF V600E or V600K mutation.
Disease is one of the following: unresectable or metastatic melanoma; limited resectable melanoma; or stage III melanoma as adjuvant or neoadjuvant therapy.
Prescribed by or in consultation with an oncologist.
Prescribed in combination with vemurafenib (Zelboraf) when indicated. Prior authorization may be required for Zelboraf.
Prescribed regimen must be FDA-approved or recommended by NCCN.
For stage III melanoma or limited resectable melanoma: member has unacceptable toxicities to the dabrafenib/trametinib (Tafinlar/Mekinist) combination or Tafinlar/Mekinist are not appropriate for the member on the basis of agent side-effect profiles (i.e., trial of Tafinlar/Mekinist unless contraindicated).
For cobimetinib (Cotellic) requests, member must use cobimetinib in combination as specified, if available, unless contraindicated or clinically significant adverse effects are experienced.
Dose does not exceed both of the following for the first 21 days of each 28-day cycle: 60 mg per day and no more than 3 tablets per day.
Dose may exceed or differ only if supported by practice guidelines or peer-reviewed literature for the relevant off-label use; prescriber must submit supporting evidence.

Initial Therapy - Histiocytic Neoplasms

Initial Approval Criteria for histiocytic neoplasms (must meet ALL):

ALL of the following

Diagnosis of a histiocytic neoplasm (examples include Langerhans cell histiocytosis [LCH], Rosai–Dorfman disease, Erdheim–Chester disease [ECD], xanthogranuloma, or mixed histiocytosis).
Prescribed by or in consultation with an oncologist or hematologist.
Age > 18 years.
Disease is one of the following: multi-system disease; recurrent or refractory disease; or single-system disease unlikely to benefit from conventional therapies.
Disease is positive for a BRAF V600E mutation and either unable to access a BRAF inhibitor or treatment with a BRAF inhibitor has been discontinued due to intolerable side effects or toxicity; OR documentation that BRAF‑mutated ECD or LCH has progressed on BRAF inhibitor therapy.

Initial Therapy - CNS Cancers (off-label, NCCN-supported)

Initial Approval Criteria for selected CNS cancers (off-label) (must meet ALL):

ALL of the following

Diagnosis of one of the following CNS tumors: 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.
Disease is positive for the BRAF V600E mutation.
Prescribed by or in consultation with an oncologist.
Prescribed in combination with vemurafenib (Zelboraf) when indicated. Prior authorization may be required for Zelboraf.
Prescribed regimen must be FDA-approved or recommended by NCCN.

Continuation Therapy

Continuation (Renewal) Criteria (must meet ALL):

ALL of the following

Member is currently receiving cobimetinib via the Centene benefit, or documentation supports that member is currently receiving cobimetinib for a covered indication and has received this medication for at least 30 days.
Member is responding positively to therapy as documented by the prescriber (clinical benefit or radiographic response).
For cobimetinib (Cotellic) requests, member must use cobimetinib in combination as specified, if available, unless contraindicated or clinically significant adverse effects are experienced.
Dose does not exceed both of the following for the first 21 days of each 28-day cycle: 60 mg per day and no more than 3 tablets per day.

Notable covered indications and updates

Notable covered indications and updates:

ALL of the following

Melanoma: criteria updated to include stage III melanoma as adjuvant therapy and limited resectable melanoma; re-induction for progression/relapse removed as of 2Q2025 (covered under unresectable or metastatic melanoma).
Histiocytic neoplasms: diagnosis broadened to allow a range of histiocytic neoplasm types per product information; NCCN-supported indications incorporated and off-label criteria converted to FDA‑approved use where applicable.
CNS cancers: NCCN-supported off-label indications expanded to include pilocytic astrocytoma, circumscribed ganglioglioma/neuroglioma/glioneuronal tumor, pleomorphic xanthoastrocytoma, recurrent/progressive circumscribed glioma, recurrent/progressive glioblastoma, recurrent/progressive high‑grade glioma, and brain metastases; terminology updated to align with NCCN (removed anaplastic glioma and outdated '2 glioma' terms).
Approval durations: commercial approvals revised to 12 months or duration of request, whichever is less; Medicaid/HIM durations specified where applicable.

Coverage is subject to the terms, conditions, exclusions, and limitations of the member's plan. This policy is a guide to medical necessity determinations and does not guarantee coverage or payment. Providers should follow plan-specific prior authorization procedures and submit supporting documentation (including evidence for off‑label uses when required).

Initial Therapy

Initial Therapy — initial dosing and prescriber requirements

Initial dosing and prescriber requirements

Initial Dosing and Prescriber: 1. Prescribed by or in consultation with an oncologist (or hematologist for histiocytic neoplasms where specified); 2. Standard dosing: 60 mg PO once daily (three 20 mg tablets) for 21 days followed by 7 days off (28‑day cycle); 3. Dose must not exceed 60 mg/day (three tablets) during the first 21 days; 4. Off‑label dosing or alternative regimens must be supported by practice guidelines or peer‑reviewed literature and the prescriber must submit supporting evidence; 5. For melanoma indications where indicated, cobimetinib is prescribed in combination with vemurafenib (Zelboraf).60 mg/day; 3 tablets/day

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

Initial therapy notes — successive review modifications and NCCN-supported uses

Initial therapy notes — successive review modifications and NCCN‑supported uses

Initial therapy modifications:

Continuation and Re‑induction Criteria

Continuation Therapy — renewal requirements

Renewal requirements

Renewal: 1. Member must be currently receiving cobimetinib via the Centene benefit or have documentation of at least 30 days of prior use for a covered indication; 2. Member must be responding positively to therapy as documented in clinical notes; 3. Use of cobimetinib if available is required unless contraindicated or clinically significant adverse effects occur; 4. Dose must not exceed 60 mg per day (three 20 mg tablets) for the first 21 days of each 28‑day cycle; off‑label dose support must be provided by guidelines or peer‑reviewed literature with prescriber evidence submission.60 mg/day; 3 tablets/day

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

Continuation / Re‑induction notes — maintenance and re‑induction considerations

Re‑induction for melanoma:

Provider Actions and Documentation

Prior Authorization

Prior Authorization and Required Clinical Information

Prior authorization is required for Cobimetinib (Cotellic). Providers must include required clinical information with the prior authorization request, including the diagnosis, documented BRAF V600E or V600K mutation status when applicable, the involvement of or consultation with an oncologist (or hematologist for histiocytic neoplasms), and prescriber information. Provide supporting clinical documentation such as office chart notes, relevant laboratory or pathology results, imaging, prior treatment history, and progress notes to demonstrate that the member meets all applicable approval criteria.

Diagnosis and BRAF V600E/V600K mutation status (when applicable)
Oncologist (or hematologist) involvement or consultation documented
Prescriber name, specialty, and contact information
Office notes, labs/pathology reports, imaging, prior treatment records, and toxicity documentation

Step Therapy

Trial or Intolerance of Alternative Targeted Agents

Providers must submit documentation that supports trials of or intolerance to alternative targeted agents where required by the criteria. For stage III melanoma or limited resectable melanoma, requests for Cobimetinib must document use of cobimetinib if available unless contraindicated or associated with clinically significant adverse effects. For certain melanoma indications, documentation of unacceptable toxicities to the dabrafenib/trametinib (Tafinlar/Mekinist) combination or clinical rationale why Tafinlar/Mekinist is not appropriate for the member is required.

Step Therapy and Prior Trials

Required prior agent or condition	Applies to
Trial of dabrafenib + trametinib (Tafinlar/Mekinist) or documented unacceptable toxicities to these agents	Stage III melanoma or limited resectable melanoma (per 2Q2023 update) — required when clinically appropriate; exceptions if agents are contraindicated or not tolerated
Inability to access a BRAF inhibitor or discontinuation of a BRAF inhibitor due to intolerable side effects, or disease progression on BRAF inhibitor therapy (documented)	Histiocytic neoplasms with BRAF V600E mutation (documentation required when BRAF-positive)
Use cobimetinib if available unless contraindicated or clinically significant adverse effects are experienced	Applies across melanoma, histiocytic neoplasms, and selected CNS tumor requests as a general requirement

Prior trial or documented intolerance	When required / context
Prior trial of dabrafenib + trametinib (Tafinlar/Mekinist)	Referenced specifically for certain melanoma settings (stage III adjuvant or limited resectable melanoma) per 2Q2023 P&T update; may be required unless contraindicated or not tolerated
Documented unacceptable toxicities to Tafinlar/Mekinist or BRAF inhibitors	Permits use of cobimetinib when BRAF inhibitors are not appropriate (histiocytic neoplasms and melanoma where applicable); documentation required
Prior trial not required if BRAF inhibitor is inaccessible or clinically inappropriate	Applies to BRAF-mutated histiocytic neoplasms when unable to access or tolerate a BRAF inhibitor per initial criteria

Quantity Limits and Dosing

Cobimetinib (Cotellic) — Dosing & Product Availability

Typical dosing regimen60 mg PO once daily (three 20 mg tablets) for 21 days followed by 7 days off in a 28-day cycle

Maximum dose (first 21 days)60 mg/day (three 20 mg tablets)

Tablet strength available20 mg tablet

Quantity limit (tablets/day)Limit: 3 tablets per day during dosing days (equates to 60 mg/day)

Billing Rule

Site-of-care and billing — confirm with plan

Definitions

Definition — BRAF

TermBRAF

DefinitionB-Raf proto-oncogene serine/threonine kinase

ContextMutations (e.g., V600E/V600K) are required for certain indications in this policy (melanoma, selected CNS tumors).

Definition — ECD

TermECD

DefinitionErdheim-Chester disease

ContextListed among histiocytic neoplasms for which cobimetinib may be used as a single agent per policy.

Background

Cobimetinib (Cotellic) is a MEK kinase inhibitor used in oncology. Per the product information and policy, it is indicated in combination with vemurafenib for adults with unresectable or metastatic melanoma harboring a qualifying BRAF V600E or V600K mutation, and as a single agent for certain histiocytic neoplasms. The usual dosing schedule referenced in the policy is 60 mg once daily (three 20 mg tablets) for 21 days followed by 7 days off in each 28-day cycle; prescribers must not exceed 60 mg/day during the first 21 days unless supported by guideline or literature with documentation. Requests must be consistent with the labeled regimen or NCCN-recommended off-label uses where specified.

Revision History

2021-01-14annual review (2Q2021)

References updated and oral oncology generic redirection language added; P&T approval recorded 05/21/2021.

2022-02-11annual review (2Q2022)

Added NCCN-supported indications for histiocytic neoplasms and central nervous system cancers; commercial approval durations revised to 12 months or duration of request; P&T approval recorded 05/22/2022.

2023-01-17template/update (RT4)

Policy Summary

PayerCentene

PolicyCobimetinib (Cotellic) coverage

Policy CodePolicy CP PHAR.380

Change TypeCriteria added/modified to align with FDA label and NCCN (material)

Effective DateNov 16, 2016

Next Review DateN/A

Key ActionPrior authorization required; provider must document diagnosis, BRAF V600E or V600K mutation status, oncologist involvement, and prescribed regimen.

SourceLink

On This Page

For cobimetinib (Cotellic) requests, member must use cobimetinib in combination as specified, if available, unless contraindicated or clinically significant adverse effects are experienced.

Dose does not exceed both of the following for the first 21 days of each 28-day cycle: 60 mg per day and no more than 3 tablets per day.

Dose may exceed or differ only if supported by practice guidelines or peer-reviewed literature for the relevant off-label use; prescriber must submit supporting evidence.

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

For cobimetinib (Cotellic) requests, member must use cobimetinib in combination as specified, if available, unless contraindicated or clinically significant adverse effects are experienced.

Dose does not exceed both of the following for the first 21 days of each 28-day cycle: 60 mg per day and no more than 3 tablets per day.

Dose may exceed or differ only if supported by practice guidelines or peer-reviewed literature for the relevant off-label use; prescriber must submit supporting evidence.

Approval duration: Medicaid/HIM: 6 months; Commercial: 12 months or duration of request, whichever is less.

Dose may exceed or differ only if supported by practice guidelines or peer-reviewed literature for the relevant off-label use; prescriber must submit supporting evidence.

Policy initial therapy criteria were modified across reviews to: add stage III melanoma as adjuvant therapy and limited resectable melanoma (2Q2023); add NCCN‑supported CNS tumor indications and expand histiocytic neoplasm language (2Q2022–2Q2023); add and later remove a melanoma re‑induction criterion (2Q2024–2Q2025).

Consult the full policy history for P&T approval dates and specific sequencing/step therapy requirements (e.g., references to trial of dabrafenib+trametinib for certain melanoma settings).

A re‑induction criterion for melanoma (for disease progression or relapse) was added in 2Q2024 per NCCN and subsequently removed in 2Q2025 because re‑induction is considered covered under the unresectable or metastatic melanoma indication; consult the full policy for prior response and timing considerations.

Refer to full policy text for detailed re‑induction timing, prior response requirements, and any exception criteria.

Maintenance considerations: Continuation and maintenance use follow the same dosing limits and requirement that members be responding to therapy; off‑label maintenance regimens must be supported by practice guidelines or literature with prescriber evidence.

Approval durations vary by line of business as noted in renewal criteria.

Document trial and outcome of Tafinlar/Mekinist where specified (or intolerance/toxicity)
If cobimetinib is available, member must use cobimetinib unless contraindicated or intolerant

Step Therapy

Step Therapy and Off‑Label Regimen Requirements

For step therapy requirements, requests for Cobimetinib in certain melanoma settings must reference prior trial of Tafinlar (dabrafenib) plus Mekinist (trametinib) per policy. If the prescriber asserts contraindication or intolerable adverse effects to Tafinlar/Mekinist, documentation of the specific adverse events or rationale must be provided. Off‑label regimens must be FDA‑approved or supported by NCCN or peer‑reviewed literature with submitted supporting evidence.

Step therapy: trial of Tafinlar (dabrafenib) + Mekinist (trametinib) when required by indication
If claiming intolerance/contraindication, submit documentation of adverse effects or clinical rationale
Off‑label use requires supporting evidence per policy (FDA or NCCN supported)

Documentation Required

Documentation, Policy Use, and Coverage Limitations

Providers must submit all documentation consistent with this clinical policy and the Health Plan's coverage documents. Coverage decisions are subject to the terms, conditions, exclusions, and limitations of the member's evidence of coverage or contract, as well as applicable state and federal requirements and Health Plan administrative policies. This policy is not a guarantee of payment; the Health Plan may change, amend, or withdraw policies as allowed by law.

Follow documentation and submission requirements in this policy and the member's coverage documents
Coverage determinations subject to plan terms, exclusions, limitations, and legal/regulatory requirements
Policy posting date may differ from Health Plan effective date; legal/regulatory requirements govern in case of discrepancy

Include site-of-care and billing details with the request as applicable; ensure billing aligns with the member's benefit and any plan-level site-of-care rules.

Confirm site of care aligns with the member's plan and billing policies
Submit claims consistent with provider contracts and plan requirements

Definition — LCH

TermLCH

DefinitionLangerhans cell histiocytosis

ContextIncluded among histiocytic neoplasms covered by the policy for single‑agent cobimetinib use when criteria met.

Definition — NCCN-supported 2A recommendation

NCCN 2A category meaningIndicates lower-level evidence but uniform NCCN consensus that the intervention is appropriate

Policy useUsed to justify selected off‑label CNS tumor indications (e.g., certain gliomas, pilocytic astrocytoma, ganglioglioma) for cobimetinib when criteria are met.

Implication for documentationOff‑label use supported by NCCN 2A should be accompanied by appropriate clinical documentation per policy requirements.

Off-label criteria for histiocytic neoplasms converted to FDA‑approved use and updated per product label, clinical trial evidence, and NCCN.

2023-02-15annual review (2Q2023)

Melanoma criteria expanded to add stage III (adjuvant) and limited resectable melanoma and to require trial of dabrafenib+trametinib (Tafinlar/Mekinist) in specified settings.

2024-02-08annual review (2Q2024)

Added re‑induction therapy indication for melanoma (disease progression/relapse) per NCCN and expanded CNS listings (pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma); P&T approval recorded 05/24/2024.

2025-02-13annual review (2Q2025)Latest

Removed melanoma re‑induction criterion (covered under unresectable/metastatic melanoma), broadened histiocytic neoplasm diagnosis language per product information, and expanded CNS indications to include circumscribed ganglioglioma/neuroglioma/glioneuronal tumor, recurrent/progressive glioblastoma and high‑grade glioma, and brain metastases; P&T approval recorded 05/25/2025.