ModifiedHealth NetPolicy CP PHAR.380

Cobimetinib (Cotellic) — Clinical Policy

Defines medical necessity, authorization, dosing, and coverage criteria for cobimetinib (Cotellic) across melanoma, histiocytic neoplasms, CNS cancers (off-label), and other indications for Health Net lines of business.

Policy Summary

PayerHealth Net

PolicyCobimetinib (Cotellic) — Clinical Policy

Policy CodePolicy CP PHAR.380

Change TypeCriteria revisions and indication additions

Effective DateNov 16, 2016

Next Review Date

Key ActionObtain prior authorization with documentation demonstrating BRAF V600E/V600K mutation and required prior therapy trials or contraindications as specified.

SourceLink

POLICY UPDATE CHANGES

Added NCCN-supported indications criteria for histiocytic neoplasms and central nervous system cancers; Commercial approval durations revised to 12 months or duration of request, whichever is less.

Melanoma criteria updated to add stage III as adjuvant therapy, limited resectable melanoma, and requirements regarding prior trial of Tafinlar/Mekinist.

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

For melanoma per NCCN, removed criterion for re-induction therapy as this is covered by unresectable or metastatic melanoma.

For histiocytic neoplasms, revised diagnosis to allow a broad range of histiocytic neoplasm types per PI.

For central nervous system cancers per NCCN, added circumscribed ganglioglioma/neuroglioma/glioneuronal tumor; recurrent or progressive glioblastoma, recurrent or progressive high-grade glioma, and brain metastases.

For melanoma, added indication for re-induction therapy for disease progression or relapse per NCCN (previous revision, later removed for certain melanoma coverage).

For CNS cancers 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adult oligodendroglioma and WHO 2,3, or 4 adult IDH-mutant astrocytoma per NCCN-supported 2A recommendation and removed outdated terminology (anaplastic glioma/2 glioma).

60 mg/dayStandard dosing regimen

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Coverage and Medical Necessity Criteria

inv-01: Initial Therapy - 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 limited resectable melanoma OR stage III melanoma as adjuvant or neoadjuvant therapy; 3) Prescribed by or in consultation with an oncologist; 4) Prescribed in combination with vemurafenib (Zelboraf) when indicated; 5) Patient is >= 18 years of age; 6) For stage III or limited resectable melanoma: for Cotellic requests, member must use cobimetinib if available unless contraindicated or clinically significant adverse effects are experienced; 7) Member has unacceptable toxicities to dabrafenib/trametinib (Tafinlar/Mekinist) or those agents are inappropriate for the member when required by criteria; 8) Dose does not exceed 60 mg per day (3 tablets) for the first 21 days of each 28-day cycle OR dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

inv-02: Initial Therapy - Histiocytic Neoplasms

Covered when ALL of the following are met

Histiocytic neoplasms criteria: 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) Disease is recurrent or refractory multi-system disease OR single-system disease unlikely to benefit from conventional therapies; 5) If disease is positive for a BRAF mutation, documentation that the member is unable to access a BRAF inhibitor OR disease has progressed on a BRAF inhibitor OR BRAF inhibitor was discontinued due to intolerable side effects/toxicity; 6) For Cotellic requests, member must use cobimetinib if available unless contraindicated or clinically significant adverse effects are experienced; 7) Dose does not exceed 60 mg per day (3 tablets) for the first 21 days of each 28-day cycle OR dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).

inv-03: Initial Therapy - CNS Cancers (Off-label)

Covered when ALL of the following are met for listed CNS tumor types

CNS cancers (off-label) criteria: 1) Diagnosis of one of the listed CNS tumors (examples include pilocytic astrocytoma; circumscribed ganglioglioma/neuroglioma/glioneuronal tumor; recurrent or progressive circumscribed glioma; pleomorphic xanthoastrocytoma (WHO grade 2); recurrent or progressive glioblastoma; recurrent or progressive high-grade glioma; brain metastases); 2) Prescribed by or in consultation with an oncologist; 3) Disease is positive for BRAF V600E mutation; 4) Prescribed in combination with vemurafenib (Zelboraf) where indicated; 5) For Cotellic requests, member must use cobimetinib if available unless contraindicated or clinically significant adverse effects are experienced; 6) Dose does not exceed 60 mg per day (3 tablets) for the first 21 days of each 28-day cycle OR dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).

inv-04: Continuation Therapy

Covered for continuation when ALL of the following are met

Continuation therapy criteria: 1) Member is currently receiving medication via Centene benefit, or documentation supports the member has been receiving Cotellic for a covered indication for at least 30 days; 2) Member is responding positively to therapy; 3) For Cotellic requests, member must use cobimetinib if available unless contraindicated or clinically significant adverse effects are experienced; 4) Dose does not exceed 60 mg per day (3 tablets) for the first 21 days of each 28-day cycle OR dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).

inv-05: Covered indications (summary)

Policy updates define covered indications per NCCN and label; coverage depends on meeting indication-specific criteria.

Melanoma indications: Includes unresectable or metastatic melanoma; stage III (adjuvant/neoadjuvant) and limited resectable melanoma. Re‑induction language was previously added for disease progression/relapse but was removed in 2Q2025 because re‑induction is covered under unresectable or metastatic melanoma criteria.

See melanoma initial therapy criteria for full requirements

Histiocytic neoplasms: Diagnosis criteria were broadened to allow a range of histiocytic neoplasm types per product labeling (PI); the indication was converted from off‑label to FDA‑approved use in earlier reviews.

See histiocytic neoplasms initial therapy criteria

Central nervous system cancers: CNS indications were updated per NCCN to include specific WHO grades and tumor types (examples: WHO grade 2 or 3 adult oligodendroglioma; WHO grade 2, 3, or 4 adult IDH‑mutant astrocytoma; pilocytic astrocytoma; circumscribed ganglioglioma/neuroglioma/glioneuronal tumor; pleomorphic xanthoastrocytoma; recurrent/progressive glioblastoma and high‑grade glioma; brain metastases) aligned to NCCN 2A recommendations.

Treatment of melanoma in patients whose tumor is BRAF wild type is not authorized under this policy. Requests for melanoma therapy with cobimetinib must document a tumor with a BRAF V600E or V600K mutation as required by the melanoma coverage criteria; absence of a qualifying BRAF mutation will result in denial per the policy exclusion.

Terminology and listed diagnoses for central nervous system indications were updated to align with the current NCCN compendium. Outdated terms such as “anaplastic glioma” and the label “2 glioma” were removed and specific tumor types and WHO grades were added per NCCN-supported recommendations (for example, WHO grade 2 or 3 adult oligodendroglioma and WHO 2, 3, or 4 adult IDH‑mutant astrocytoma and additional circumscribed glioneuronal tumor types). Refer to the CNS criteria section for the complete, updated list of included tumor types.

Uses of cobimetinib that are not listed among the policy’s approved indications or the NCCN‑supported off‑label CNS tumor indications should be routed according to the Health Plan’s formulary and off‑label policies. For drugs that are on the formulary/PDL, follow the relevant no‑coverage policy for the line of business; for non‑formulary requests follow the non‑formulary policy. If the requested use is not specifically addressed in this policy and does not meet an exclusion, refer the request to the applicable off‑label use policy for the member’s line of business for review.

This clinical policy provides guidance to support medical necessity determinations but does not guarantee coverage or payment. Coverage decisions remain subject to the member’s benefit documents, including all terms, conditions, exclusions, and limitations, as well as applicable state and federal requirements and Health Plan administrative policies.

Initial Therapy — Condition-Specific Requirements

inv-23: Initial Therapy

Initial therapy coverage conditions

Initial therapy general: Diagnosis-specific criteria must be met per indication (melanoma, histiocytic neoplasms, or NCCN‑supported CNS tumors); prescribed by or in consultation with an oncologist (or hematologist for histiocytic neoplasms); adult age requirement as specified; BRAF V600E or V600K mutation required where specified; melanoma and some CNS indications require combination with vemurafenib where indicated; dosing limits of 60 mg/day (3 tablets) for the first 21 of each 28‑day cycle apply unless an alternative 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.

Melanoma initial therapy considerations: Melanoma criteria include specific staging (unresectable/metastatic, limited resectable, stage III adjuvant/neoadjuvant) and prior‑therapy expectations (e.g., documentation of unacceptable toxicities to or inability to use dabrafenib/trametinib when required by the indication).

See melanoma initial therapy criteria for detail

inv-24: Initial therapy

Continuation and Re-induction Criteria

inv-25: Continuation Therapy

Criteria for continued coverage

Continuation: 1) Member is currently receiving Cotellic via the Centene benefit or documentation supports prior receipt for a covered indication for at least 30 days; 2) Member is responding positively to therapy; 3) For Cotellic requests, member must use cobimetinib if available unless contraindicated or clinically significant adverse effects are experienced; 4) Dosing does not exceed 60 mg per day (3 tablets) for the first 21 days of each 28‑day cycle OR dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).

inv-26: Continuation / Re-induction

Continuation and re‑induction rules modified across reviews

Re-induction and continuation updates: Re‑induction for melanoma was previously added for disease progression or relapse per NCCN but was removed in 2Q2025 because re‑induction is considered covered under unresectable or metastatic melanoma. Continuation and re‑induction rules have been otherwise adjusted to reflect NCCN and label changes over time.

Provider Requirements and Administrative Actions

Prior Authorization

Prior Authorization Required

Prior authorization is required. Providers must ensure the member meets the diagnosis and all clinical criteria in the policy before submitting requests.

Prior authorization required for Cotellic (cobimetinib) for covered indications.
Prescribed regimen must be FDA‑approved or recommended by NCCN; off‑label uses require supporting literature.
When used in combination regimens (e.g., with Zelboraf/ vemurafenib), prior authorization may also be required for the companion agent.

Prior Authorization

Prior Authorization and Approval Durations

Prior authorization requirements and approval durations may vary by member product. Approval durations in the source: Medicaid/HIM — 6 months; Commercial — 12 months or duration of request, whichever is less. Check plan-specific administrative rules for exact approval lengths.

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

Step Therapy and Prior Treatment Tables

Requirement	Applies to
Trial of or documented unacceptable toxicities to dabrafenib + trametinib (Tafinlar/Mekinist), or those agents are not appropriate for the member based on side-effect profile
Required for certain melanoma indications (stage III or limited resectable melanoma per melanoma initial criteria) and for histiocytic neoplasm indications when specified

Documentation to submit	Notes
Provider must submit documentation (office chart notes, lab results, or other clinical information) supporting prior therapy trial or intolerance to prior agents
Document prior trial or documented intolerance where specified in criteria (e.g., melanoma stage III/limited resectable and histiocytic neoplasms); prior trial expectations were added/updated in recent reviews per NCCN guidance

Dosing Limits, Product Availability, and Quantity Limits

Dose limit

Dose limit60 mg/day; not to exceed 3 tablets per day for the first 21 days of each 28-day cycle

Cycle scheduleAdminister 60 mg (three 20 mg tablets) once daily for 21 days followed by 7 days off in a 28‑day cycle

Maximum per day60 mg (3 tablets) — do not exceed this dose during the 21 days on treatment

Cobimetinib (Cotellic) — dosing & quantity limit

DrugCobimetinib (Cotellic)

Standard dosing60 mg/day (three 20 mg tablets) given once daily for 21 days followed by 7 days off (28‑day cycle)

Drug Background and Definitions

Cobimetinib (Cotellic) is a MEK kinase inhibitor. The product is available as oral tablets (20 mg) and the standard labeled dosing regimen used in melanoma and many covered indications is 60 mg per day (three 20 mg tablets) on days 1–21 of each 28‑day cycle. The drug is indicated in combination with vemurafenib for unresectable or metastatic melanoma with a qualifying BRAF V600E or V600K mutation, and single‑agent cobimetinib use has been incorporated for adult histiocytic neoplasms per labeling and policy updates; selected CNS tumor indications with BRAF V600E mutation are included per NCCN‑supported recommendations.

BRAF — definition

DefinitionBRAF = B‑Raf proto‑oncogene serine/threonine kinase

Gene roleOncogene encoding a serine/threonine kinase involved in MAPK signaling

Relevance to policyPresence of BRAF V600E or V600K mutation is required for melanoma and selected CNS tumor coverage per criteria

Histiocytic disease abbreviations

Site of Care Considerations

Note

Site of care: infusion center

Infusion center site-of-care notation: when applicable, Cotellic use and requests should follow the plan's site-of-care guidance (policy lists 'infusion center' as a relevant setting).

Ensure claims and authorization requests reflect the correct site of care per Health Plan requirements.

Revision and Approval History

2023-02-15material revision

Melanoma criteria updated to add stage III as adjuvant therapy, limited resectable melanoma, and requirements for prior trial of Tafinlar/Mekinist.

2023-01-17material revision

Off-label criteria for histiocytic neoplasms converted to FDA‑approved use and updated per product label, clinical trial evidence, and NCCN guidance (RT4).

2022-02-11material revision