CurrentEmblemHealthPolicy MG.MM.PH.79

Erbitux (cetuximab) Intravenous

Clinical coverage criteria and ICD-10 diagnosis codes relevant to cetuximab (Erbitux) for various solid tumors (colorectal, head and neck, NSCLC, skin cancers, etc.) for members of EmblemHealth/ConnectiCare.

Policy Summary

PayerEmblemHealth

PolicyErbitux (cetuximab) Intravenous

Policy CodePolicy MG.MM.PH.79

Change TypeMultiple substantive revisions (biomarkers, regimens, metastatic scenarios)

Effective Date

Next Review DateApr 10, 2025

Key ActionObtain prior authorization and submit documentation of tumor site, prior systemic therapies, and mutation testing (BRAF, KRAS/NRAS, EGFR) when requesting cetuximab for colorectal cancer indications.

SourceLink

POLICY UPDATE CHANGES

Added approval option for patients with unresectable synchronous liver and/or lung metastases and for patients with unresectable metachronous metastases in colon and rectal cancer.

Removed requirement that tumors be wild-type BRAF and removed prior chemotherapy requirement for certain CRC approvals; added BRAF and KRAS mutation-specific conditions including BRAF V600E and KRAS G12C.

Added combinations of Erbitux with immune checkpoint inhibitors (pembrolizumab/Keytruda and nivolumab/Opdivo) and with taxanes (paclitaxel or docetaxel) for head and neck squamous cell carcinoma.

Expanded Cetuximab use language for head and neck cancers to include multiple regimen scenarios (first-line, subsequent therapy, single agent sequential chemoradiation, combination with platinum agents, etc.) and replaced 'Cancer of the Lip' with 'Cancer of the Oral Cavity (including mucosal lip)'.

Modified NSCLC criteria to cover recurrent, advanced, or metastatic disease with known sensitizing EGFR mutation and receipt of at least one tyrosine kinase inhibitor; removed stricter prior metastatic-only language.

20+ICD-10 codes listed

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Tumor groups covered

Coverage Criteria and Medical Necessity

Covered indications and regimen-pathways

Covered when criteria for specific tumor type, biomarker status, regimen, and prior therapy are met as outlined below.

Head and Neck Squamous Cell Carcinoma (SCCHN): Patient meets ONE of the allowed regimen scenarios: Erbitux (cetuximab) may be used in combination with paclitaxel or docetaxel; may be used in combination with pembrolizumab (Keytruda) or nivolumab (Opdivo); may be used as first-line or subsequent therapy; may be used as a single agent for certain non‑nasopharyngeal cancers; or may be used in combination with platinum-based therapy depending on tumor site and clinical scenario.

Non‑Small Cell Lung Cancer (NSCLC): Patient has recurrent, advanced, or metastatic NSCLC with a known sensitizing EGFR mutation and has received at least ONE tyrosine kinase inhibitor; cetuximab combinations for specific scenarios are covered per the revised criteria.

The policy language has been revised to remove prior blanket exclusions related to adjuvant use and to adjust prior-therapy requirements for colorectal cancer (CRC). Specifically, the prior criterion requiring tumors or metastases to be BRAF wild-type and the requirement that the patient had previously received a chemotherapy regimen for colon or rectal cancer were removed. The CRC pathways now include new approval options for patients with unresectable synchronous liver and/or lung metastases and for patients with unresectable metachronous metastases. In addition, the policy adds explicit mutation-specific pathways (for example, BRAF V600E and KRAS G12C) and expands where cetuximab may be used (including as a single agent or in specific combinations such as with FOLFOX, CapeOX, or FOLFIRI) depending on the tumor and clinical scenario.

Requests will be considered not medically necessary when they do not meet the policy’s biomarker, regimen, or sequencing requirements. Examples include absence of required mutation testing or documentation (eg, BRAF, KRAS/NRAS), use in a CRC pathway that requires a specific mutation status but the tumor does not meet that status, or prescribing cetuximab outside the allowed combination regimens or sequencing (for example, when an encorafenib combination is required for BRAF V600E disease or when prior-line requirements for subsequent therapy are not satisfied). Such nonconforming requests are subject to denial or clarification per the policy.

Regimens and Combination Therapies

Indication	Allowed combinations / settings	Coverage status
Squamous cell carcinoma of the head and neck (SCCHN)
Cetuximab in combination with paclitaxel or docetaxel; cetuximab in combination with pembrolizumab (Keytruda) or nivolumab (Opdivo); may be used as first-line or subsequent therapy, as single agent for certain non-nasopharyngeal cancers, or in combination with platinum-based therapy depending on tumor site and clinical scenario
Notes: regimen options expanded in revision history to include taxanes and immune checkpoint inhibitors; site/subtype language clarified

Indication	Allowed combination	Coverage status
Colorectal cancer with BRAF V600E mutation
Cetuximab used in combination with encorafenib
Conditions: BRAF V600E must be determined by an FDA‑approved or CLIA‑compliant test; use as subsequent therapy after at least one prior line for advanced/metastatic disease OR as primary treatment for unresectable metastatic disease after prior adjuvant FOLFOX/CapeOX within the past 12 months

Indication	Allowed chemotherapy backbone(s)	Coverage status
Metastatic or unresectable colorectal cancer (selected pathways)
Cetuximab used with FOLFIRI, FOLFOX, or other irinotecan- or oxaliplatin-based regimens per pathway (including use as primary treatment or subsequent therapy and single-agent options for refractory/intolerant disease)
Additional details: pathways specify use for oxaliplatin- or irinotecan-refractory disease (cetuximab ± appropriate backbone), and prior adjuvant FOLFOX/CapeOX within 12 months affects some primary treatment allowances

Biomarker and Mutation Requirements

BRAF (including V600E)

BRAF V600E positiveWhen BRAF V600E mutation is present, cetuximab is allowed in combination with encorafenib; approved as subsequent therapy after at least one prior line for advanced/metastatic disease, or as primary treatment for unresectable metastatic disease after prior adjuvant FOLFOX/CapeOX within the past 12 months.

BRAF mutation negative (wild-type)For metastatic/unresectable BRAF mutation–negative disease, cetuximab may be used as primary treatment in combination with FOLFIRI, FOLFOX, or irinotecan-based regimens; also allowed as subsequent therapy per regimen-specific refractory/intolerance pathways.

Testing requirementBRAF mutation status must be determined by an FDA‑approved or CLIA‑compliant test to establish V600E positivity when required for the encorafenib combination pathway.

KRAS/NRAS (including KRAS G12C)

KRAS/NRAS mutation-negative pathwayPolicy includes condition of approval for KRAS/NRAS/BRAF mutation–negative disease for certain CRC subsequent treatment pathways.

Line of Therapy and Sequencing

first-line | second-line | subsequent

Authorization depends on line of therapy as specified below.

CRC lines

First-line: Used as primary treatment in combination with FOLFIRI or FOLFOX (or CapeOX where specified) for eligible patients per mutation and clinical scenario (eg, BRAF wild-type pathway permitting primary combination use).
Subsequent / later-line: Used as subsequent therapy in combination regimens for refractory disease (eg, irinotecan- or oxaliplatin-refractory disease), or as the cetuximab + encorafenib combination for BRAF V600E disease after at least one prior line in the advanced/metastatic setting; also allowed as primary treatment for unresectable metastatic BRAF V600E disease after prior adjuvant FOLFOX/CapeOX within 12 months per the pathway.

Head and Neck (SCCHN) lines: Erbitux may be authorized as first-line or subsequent therapy, or as single-agent therapy for specified non‑nasopharyngeal tumors, and in combination regimens (eg, with taxanes or immune checkpoint inhibitors) as described in the policy.

Diagnosis Codes and Coding Notes

ICD-10 Diagnoses (selected)ICD-10

C00.0	Malignant neoplasm of external upper lip
C00.1	Malignant neoplasm of external lower lip
C02.9	Malignant neoplasm of tongue, unspecified
C03.9	Malignant neoplasm of gum, unspecified
C04.9	Malignant neoplasm of floor of mouth, unspecified
C05.0	Malignant neoplasm of hard palate
C06.9	Malignant neoplasm of mouth, unspecified
C09.9	Malignant neoplasm of tonsil, unspecified
C10.9	Malignant neoplasm of oropharynx, unspecified
C11.9	Malignant neoplasm of nasopharynx, unspecified

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Prior adjuvant window for CRC primary treatment after adjuvant FOLFOX/CapeOX

Time window after adjuvant FOLFOX/CapeOXPrimary treatment pathway after prior adjuvant FOLFOX or CapeOX is allowed if the adjuvant therapy was within the past 12 months.

Applicable regimensThis 12‑month window is referenced specifically for use of cetuximab in combination with FOLFIRI, FOLFOX, or irinotecan-based regimens in CRC primary treatment pathways.

Purpose of windowDefines eligibility for primary unresectable metastatic CRC after recent adjuvant oxaliplatin-containing therapy.

Prior Authorization, Documentation, and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for cetuximab and similar agents when used for colorectal cancer indications. Approval depends on tumor sidedness, KRAS/NRAS/BRAF mutation status, prior lines of therapy, and the specific regimen requested. Providers must obtain PA before initiating therapy.

Prior authorization required for CRC indications where regimen or biomarker criteria apply
Criteria tied to tumor sidedness (left vs right), KRAS/NRAS/BRAF mutation status, and intended combination regimen

Denial Risk

CRC Biomarker/Regimen Nonconformance — Denial Risk

Requests that do not meet the revised biomarker, prior therapy, or regimen requirements are at high risk for denial. Common nonconformance scenarios include: absence of documented tumor origin (colon vs rectum), missing KRAS/NRAS/BRAF mutation testing results, requesting single-agent use in biomarker-defined settings that require combination therapy, or using the agent as first-line therapy when policy requires prior exposure to an oxaliplatin- and/or irinotecan-based regimen.

Key Definitions

Synchronous metastases

DefinitionMetastases diagnosed at the same time as or within a few months of the initial diagnosis of colon or rectal cancer.

ContextUsed to identify synchronous liver and/or lung metastases as an approval pathway for unresectable disease.

Implication for treatmentSynchronous metastases may qualify patients for the newly added CRC approval option for unresectable metastatic disease.

Metachronous metastases

DefinitionMetastases diagnosed months to years after the initial diagnosis of colon or rectal cancer.

ContextPolicy added approval option for patients with unresectable metachronous metastases in colon and rectal cancer.

Background

Cetuximab (Erbitux) is an anti–EGFR monoclonal antibody indicated for use in multiple solid tumor settings. The policy references cetuximab’s role in colorectal cancer and in squamous cell carcinoma of the head and neck, and links coverage to tumor site, prior systemic therapies, and relevant biomarker status (for example, KRAS/NRAS/BRAF in CRC and sensitizing EGFR mutations in non–small cell lung cancer).

Revision History and Policy Changes

2025-04-10annual review - material clinical changesLatest

Added approval options for unresectable synchronous and metachronous liver/lung metastases in colorectal cancer; removed BRAF wild-type and prior chemotherapy requirements for certain CRC pathways; added BRAF V600E and KRAS G12C-specific conditions and expanded CRC sequencing rules.

2024-03-13annual review - regimen expansion

Added approval of cetuximab in combination with paclitaxel or docetaxel and with pembrolizumab (Keytruda) or nivolumab (Opdivo) for head and neck squamous cell carcinoma; added metachronous metastases definition and other SCCHN regimen clarifications.

Policy Summary

PayerEmblemHealth

PolicyErbitux (cetuximab) Intravenous

Policy CodePolicy MG.MM.PH.79

Change TypeMultiple substantive revisions (biomarkers, regimens, metastatic scenarios)

Effective Date

Next Review DateApr 10, 2025

SourceLink

On This Page

KRAS G12C mutation positiveKRAS G12C mutation–positive disease is specifically added as a condition of approval in the revised CRC criteria.

Documentation neededMutation status (KRAS/NRAS, including specific variants such as KRAS G12C) must be documented to support CRC indication and regimen selection.

EGFR sensitizing mutations

Exon 19 deletionExample of an EGFR sensitizing mutation used to qualify NSCLC patients for the cetuximab pathway.

Exon 21 L858RExample of an EGFR sensitizing mutation listed in the NSCLC criteria.

Other sensitizing variants (S768I, L861Q, etc.)EGFR S768I and L861Q are cited as additional examples of sensitizing EGFR mutations in the policy.

NSCLC lines: For NSCLC with sensitizing EGFR mutations, cetuximab coverage requires prior receipt of at least one tyrosine kinase inhibitor (ie, subsequent to TKI therapy) as specified in the revised criteria.

Missing or undocumented KRAS/NRAS/BRAF mutation status (must be from FDA-approved or CLIA-compliant test)
Requesting therapy inconsistent with tumor sidedness guidance (e.g., right-sided disease where anti-EGFR agents are not recommended)
Regimen nonconformance: using single-agent when combination with FOLFOX, CapeOX, or FOLFIRI is required for the indication
Prior therapy nonconformance: no documentation of required prior oxaliplatin- and/or irinotecan-based regimen when policy requires prior exposure

Step Therapy

Sequencing / Step Therapy Requirements

Sequencing and step therapy requirements apply for certain colorectal cancer indications. Approval may be contingent on prior lines of therapy or documented intolerance to specific agents. Examples: patients must have progressed on or been intolerant to oxaliplatin- and irinotecan-based regimens for some subsequent-therapy approvals; BRAF V600E–positive disease approvals may require prior systemic therapy unless used in combination with encorafenib as specified; KRAS G12C or other mutation–specific indications follow the sequencing outlined in criteria.

Must document prior exposure and/or failure on oxaliplatin- and irinotecan-based regimens when required (or intolerance to irinotecan)
Allowable sequencing: use in combination with FOLFIRI, FOLFOX, or irinotecan-based regimens per indication and prior-adjuvant timing (e.g., progression within 12 months of adjuvant FOLFOX/CapeOX may influence sequencing)
BRAF V600E: use in combination with encorafenib as subsequent therapy after at least one prior line for advanced/metastatic disease, or as primary treatment for unresectable metastatic disease following prior adjuvant therapy within 12 months when specified
Policy may permit single-agent use only in clearly defined refractory or intolerant situations

Documentation Required

Required Clinical Documentation

Documentation required with PA requests: tumor origin (colon vs rectum), sidedness (left vs right), KRAS/NRAS/BRAF mutation test results (report and testing method), prior chemotherapy regimens with dates and responses, reasons for intolerance if cited, and the exact regimen requested including combination agents and intent (first-line vs subsequent). Lack of these documents may delay or result in denial.

Tumor origin and sidedness (left vs right) clearly documented
KRAS, NRAS, and BRAF mutation status with test type (FDA-approved or CLIA-compliant) and result
Detailed prior therapy history: agents, dates, responses, and reasons for discontinuation or intolerance
Planned regimen details (e.g., combination with FOLFIRI, FOLFOX, CapeOX, encorafenib) and line of therapy being requested

Implication for treatmentMetachronous metastases are included as an eligibility scenario for cetuximab pathways in CRC per the revisions.

2023-07-05annual review - NSCLC criteria update

Modified NSCLC criteria to cover recurrent, advanced, or metastatic disease with a known sensitizing EGFR mutation and receipt of at least one tyrosine kinase inhibitor; removed prior metastatic-only language and clarified mutation and TKI examples.

2022-04-26administrative update with content changes

Template transfer and policy content updates including expanded head and neck regimen language and other clarifications (dosage chart updated).