CurrentAnthemPolicy CC-0106

Erbitux (cetuximab) — Clinical coverage criteria

Clinical coverage criteria for Erbitux (cetuximab) describing medically necessary indications, limits, and coding for Anthem medical benefit members, focused on colorectal cancer, squamous cell carcinomas, and related uses.

Policy Summary

PayerAnthem

PolicyErbitux (cetuximab) — Clinical coverage criteria

Policy CodePolicy CC-0106

Change TypeRevised (material clinical updates)

Effective Date

Next Review DateMay 16, 2025

Key ActionObtain prior authorization and document diagnosis plus required molecular test results (e.g., RAS/BRAF or specified EGFR mutations) to support coverage.

SourceLink

POLICY UPDATE CHANGES

Updated colon, rectal, colorectal, appendiceal or anal adenocarcinoma criteria and added persistent and high-risk regional disease of squamous cell carcinoma of the head and neck.

Updated squamous cell cancer of skin and penile cancer criteria and adjusted ICD-10 code list (added C33, C44.1291-C44.1292; removed several codes).

J9055HCPCS

2ANCCN level

Black boxSafety

NCState

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Initial/advanced colorectal cancer

Covered when ALL of the following are met for colon, rectal, colorectal, appendiceal or anal adenocarcinoma:

Colorectal adenocarcinoma approval: Individual has a diagnosis of colon, rectal, colorectal, appendiceal or anal adenocarcinoma; AND individual has unresectable, recurrent, progressive, advanced or metastatic disease; AND individual has gene mutation testing with one of the following results: RAS wild-type OR BRAF wild-type; OR for certain settings the individual has BRAF V600E OR KRAS G12C when cetuximab is used as part of a combination therapy.molecular testing result required

Matches NCCN 2A recommendations and label specifics

SCCHN — multiple covered indications

Covered when ANY of the following established SCCHN indications are met:

SCCHN indications: Cetuximab is used in one of the following: (1) in combination with radiation therapy for locally or regionally advanced disease; OR (2) in combination with chemotherapy for first-line treatment of recurrent locoregional or metastatic disease; OR (3) as a single agent for recurrent or metastatic disease in individuals for whom prior platinum-based therapy has failed; OR (4) treatment for persistent, recurrent unresectable, or metastatic SCCHN; OR (5) as sequential therapy in combination with radiation; OR (6) as a single agent or in combination therapy with or without radiation for second primary after prior radiation, resectable locoregional recurrence without prior radiation, or high-risk regional disease (NCCN 2A).clinical scenario per list

Includes persistent and high-risk regional disease added in 05/16/2025

Squamous cell skin / penile

Covered when ALL of the following are met for squamous cell skin carcinoma or penile squamous cell carcinoma:

SCC skin/penile: Individual has a diagnosis of squamous cell skin carcinoma or penile squamous cell carcinoma; AND disease is unresectable or locally advanced, recurrent, or metastatic; AND use is consistent with NCCN 2A recommendations for advanced disease.disease extent

NCCN 2A guidance for inoperable positive regional nodes, regional recurrence, or distant metastases

NSCLC — biomarker-driven

Covered when ALL of the following are met for NSCLC (per NCCN 2A listing):

NSCLC with EGFR mutation: Individual has recurrent, advanced or metastatic non-small cell lung cancer; AND molecular testing documents one of the specified EGFR activating mutations: exon 19 deletion, exon 21 L858R, S768I, L861Q, or G719X; AND cetuximab is being used in combination with afatinib as subsequent therapy per NCCN 2A listing.specified EGFR mutations and combination with afatinib

Follows NCCN 2A listing in policy

Requests for Erbitux (cetuximab) will be denied when they are submitted for all other indications not listed in the covered criteria. The policy explicitly disallows use of cetuximab in combination with other monoclonal antibodies and prohibits approval when combined with anti-VEGF agents (bevacizumab, ziv-aflibercept, or ramucirumab). These exclusions apply regardless of line of therapy and are intended to align authorization decisions with the specific indications and combination regimens described in the coverage criteria.

The policy does not support use of Erbitux as adjuvant therapy after resection for colon cancer. Clinical trial data (Alberts 2012) and current guideline interpretation led to halting of the adjuvant trial and to NCCN guidance stating Erbitux has no role in the adjuvant treatment of colon cancer at this time. Therefore requests for cetuximab in the adjuvant post‑resection setting will not be approved.

Additional guidance: prior treatment with the other anti‑EGFR monoclonal antibody panitumumab is a disqualifying factor for approval (prior panitumumab therapy -> not approved), although a prior course of panitumumab discontinued for an adverse reaction is not considered prior treatment for purposes of this policy. Requests should include documentation of mutation testing and prior therapies to support clinical appropriateness per the covered indications.

Regimens and Combination Use

Regimen	Indication / Required criteria	Coverage status
{"text":"Cetuximab plus radiation","status":""},{"text":"Locally or regionally advanced squamous cell carcinoma of the head and neck (SCCHN) — used in combination with radiation for initial treatment per FDA label and NCCN 2A","status":"covered"},{"text":"","status":""}
{"text":"Cetuximab plus chemotherapy","status":""},{"text":"First-line treatment of recurrent locoregional or metastatic SCCHN in combination with chemotherapy per FDA label and NCCN 2A","status":"covered"},{"text":"","status":""}
{"text":"Single‑agent cetuximab","status":""},{"text":"Recurrent or metastatic SCCHN after prior platinum‑based chemotherapy has failed (single‑agent use per FDA label and NCCN 2A)","status":"covered"},{"text":"","status":""}

Regimen	Indication / Required criteria	Coverage status
{"text":"Cetuximab in combination with chemotherapy","status":""},{"text":"Metastatic colorectal cancer — individual has unresectable, recurrent, progressive, advanced or metastatic disease and gene mutation testing shows RAS wild‑type or BRAF wild‑type (NCCN 2A; FDA‑approved combinations)","status":"covered"},{"text":"","status":""}
{"text":"Single‑agent cetuximab","status":""},{"text":"Metastatic colorectal cancer — as single agent for RAS wild‑type/BRAF wild‑type disease per FDA labeling and NCCN 2A when criteria met","status":"covered"},{"text":"","status":""}
{"text":"Cetuximab plus encorafenib","status":""},{"text":"BRAF V600E–mutated metastatic colorectal cancer after prior therapy — combination with encorafenib as FDA‑approved regimen","status":"covered"},{"text":"","status":""}

Regimen	Policy guidance / Rationale	Coverage status
{"text":"Cetuximab combined with bevacizumab (anti‑VEGF)","status":""},{"text":"Concurrent use of an anti‑EGFR agent (cetuximab) with an anti‑VEGF agent (bevacizumab) is strongly recommended against by NCCN and has shown no improved outcomes with increased toxicity (e.g., Tol 2009). Policy does not approve cetuximab used in combination with anti‑VEGF agents.","status":"not_covered"},{"text":"","status":""}
{"text":"Cetuximab combined with ziv‑aflibercept or ramucirumab","status":""},{"text":"Concurrent use with other anti‑VEGF monoclonal antibodies (ziv‑aflibercept, ramucirumab) is considered non‑approved per policy; requests for such combinations will not be approved.","status":"not_covered"},{"text":"","status":""}
{"text":"Cetuximab combined with other monoclonal antibodies","status":""},{"text":"Policy prohibits use of Erbitux in combination with another monoclonal antibody (concurrent biologic combinations); such combinations are excluded from approval and may increase toxicity without benefit.","status":"not_covered"},{"text":"","status":""}

Billing and Diagnosis Codes

HCPCSHCPCS

J9055

Injection, cetuximab, 10 mg [Erbitux]

ICD-10 Diagnosis (group 1)ICD-10

C09.0-C14.8	Malignant neoplasm of lip and oral cavity
C18.0-C20	Malignant neoplasm of colon, rectosigmoid junction, rectum
C21.0-C21.8	Malignant neoplasm of anus and anal canal
C30.0	Malignant neoplasm of nasal cavity
C31.0-C31.1	Malignant neoplasm of paranasal sinuses
C32.0-C32.9	Malignant neoplasm of larynx
C33	Malignant neoplasm of trachea
C34.00-C34.92	Malignant neoplasm of bronchus and lung
C44.02	Squamous cell carcinoma of skin of lip
C44.1291-C44.1292	Squamous cell carcinoma of skin of eyelid, including canthus

1–10 of 20

1/2

ICD-10 Diagnosis (group 2)ICD-10

C77.0	Secondary and unspecified malignant neoplasm of lymph nodes of head, face and neck
C78.5	Secondary malignant neoplasm of large intestine and rectum
C79.2	Secondary malignant neoplasm of skin
Z51.11-Z51.12	Encounter for antineoplastic chemotherapy and immunotherapy
Z85.038	Personal history of other malignant neoplasm of large intestine
Z85.048	Personal history of other malignant neoplasm of rectum, rectosigmoid junction, and anus
Z85.810-Z85.819	Personal history of malignant neoplasm of lip, oral cavity and pharynx
Z85.118	Personal history of other malignant neoplasm of bronchus and lung

Molecular test results

Colorectal molecular requirementRAS wild-type OR BRAF wild-type required for colorectal/appendiceal/anal adenocarcinoma (gene mutation testing must be done).

Colorectal combination exceptionBRAF V600E or KRAS G12C allowed only when used as part of combination therapy for unresectable, progressive, advanced, or metastatic disease.

NSCLC EGFR mutationsFor recurrent, advanced or metastatic NSCLC when cetuximab is used with afatinib: specified activating EGFR mutations required (see EGFR activating mutations list).

Provider Requirements and Operational Notes

Prior Authorization

Prior Authorization Required

Prior authorization is required. Approvals will be granted only when the request meets the policy's clinical criteria for the specified diagnosis and required molecular test results.

Prior authorization required for Erbitux (cetuximab) per payer policy.
Approvals contingent on diagnosis and documented molecular testing (e.g., RAS, BRAF, EGFR mutations) as specified in coverage criteria.

Step Therapy

Therapy Sequencing and Combination Limits

Erbitux must not be used in combination with another monoclonal antibody and should not be used as a switch after failure of another anti-EGFR agent (e.g., panitumumab). Do not use Erbitux concurrently with anti-VEGF agents (bevacizumab, ziv‑aflibercept, ramucirumab).

Do not combine Erbitux with another monoclonal antibody.
Policy advises against switching to Erbitux after failure of another anti‑EGFR agent; a prior course of panitumumab discontinued for adverse reaction (not progression) is not considered prior treatment.
Concurrent use of Erbitux with anti‑VEGF therapy is not allowed.

Documentation Required

Required Clinical Documentation

Providers must document the diagnosis and supporting clinical information to establish medical necessity.

Documented diagnosis (e.g., colorectal adenocarcinoma, SCCHN, squamous cell skin carcinoma, penile squamous cell carcinoma, NSCLC) and disease status (unresectable, recurrent, metastatic, or locally advanced).
Document prior therapies and lines of treatment (including platinum-based therapy, prior anti‑EGFR therapy such as panitumumab, and whether panitumumab was discontinued for adverse reaction versus progression).
Provide relevant molecular test results as applicable to the indication: RAS (KRAS/NRAS) wild‑type or mutation status, BRAF (including V600E) status, EGFR mutations (exon 19 deletion, L858R, S768I, L861Q, G719X), KRAS G12C when required by the criteria.
If requesting use in combination regimens, specify all agents, regimen intent (initial vs subsequent therapy), and evidence that combination is allowed per policy criteria.
Include documentation of intent to use with radiation or as sequential therapy when applicable (e.g., SCCHN indications).

Denial Risk

Common Denial Triggers

Requests may be denied for missing or incomplete documentation, for indications not listed in the policy, or for disallowed combinations/sequencing.

Denial risk if required molecular testing (RAS, BRAF, EGFR) is not documented when required by the coverage criteria.
Denial risk for use in combination with other monoclonal antibodies or with anti‑VEGF agents.
Denial risk for indications not specified in the policy (including adjuvant use after colon cancer resection) or prior receipt of panitumumab when prohibited.

Molecular and Biomarker Requirements

RAS (KRAS/NRAS) requirement

RequirementRAS (KRAS/NRAS) must be wild-type (no KRAS or NRAS mutations) for colorectal cancer coverage.

RationaleMutations in KRAS and NRAS predict lack of response to Erbitux therapy for colorectal cancer.

DocumentationGene mutation testing must be performed and results documented in the medical record before approval.

BRAF requirement

Primary requirementBRAF wild-type is required for colorectal cancer coverage (BRAF gene normal or lacking mutations).

Exception for combination therapyBRAF V600E may be accepted when cetuximab is used in combination with encorafenib after prior therapy (combination regimen required).

Clinical noteIn the presence of BRAF mutations, response to EGFR inhibitors is very unlikely unless given with a BRAF inhibitor.

EGFR activating mutations

Listed EGFR activating mutationsExon 19 deletion; exon 21 L858R; S768I; L861Q; G719X.

Context of useRequired for NSCLC coverage when cetuximab is used in combination with afatinib for recurrent, advanced, or metastatic disease.

DocumentationProvider must document specific EGFR mutation test result in the medical record for authorization consideration.

Background and Drug Information

Erbitux (cetuximab) is a recombinant human/mouse chimeric monoclonal antibody that targets and inhibits the biologic activity of the epidermal growth factor receptor (EGFR). It is FDA‑approved for treatment of colorectal cancer (as single agent, in combination with chemotherapy, and in combination with encorafenib for BRAF‑mutated disease after prior therapy) and for squamous cell carcinoma of the head and neck (SCCHN) with label indications that include combination with radiation for initial treatment, combination with chemotherapy for first‑line recurrent/metastatic disease, and single‑agent use for recurrent/metastatic disease after prior chemotherapy has failed. Efficacy in colorectal cancer is dependent on RAS/BRAF mutation status, and the agent carries important safety warnings including infusion reactions and cardiopulmonary arrest that require monitoring.

Policy Revision History

2025-05-16Annual ReviewLatest

Updated colon, rectal, colorectal, appendiceal or anal adenocarcinoma criteria and added persistent and high-risk regional disease of squamous cell carcinoma of the head and neck; coding reviewed with no changes.

2025-03-10Select Review

Updated squamous cell cancer of skin and penile cancer criteria and adjusted ICD-10 code list (added C33, C44.1291-C44.1292; removed several codes).

2024-09-09Select Review

Removed NSCLC from 'may not approve' criteria; coding reviewed with no changes.

2024-05-17Annual Review

Added colorectal cancer mutations (K12C, POLE/MMR, dMMR/MSIH), added NSCLC and penile cancer to squamous cell carcinoma, removed anal cancer from 'do not approve' criteria; coding updates added ICD-10-CM C34.00-C34.92, C60.0-C60.9, Z85.118.

2023-05-19Annual Review

Modified colorectal criteria to match NCCN wording; coding reviewed with no changes.

OpenPayer