Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Cetuximab (Erbitux®)
Policy #:MA08.031d

This policy is applicable to the Company’s Medicare Advantage products only. Policies that are applicable to the Company’s commercial products are accessible via a separate commercial policy database.


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.


This Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

COLORECTAL CANCER
Cetuximab (Erbitux®) for colorectal cancer is considered medically necessary and, therefore, covered for the following indications when all of the inclusion criteria listed below and the dosing and frequency requirements listed in Attachment A are met and none of the exclusion criteria listed below are present:

Inclusion Criteria

Metastatic Colorectal Cancer (mCRC)
Cetuximab (Erbitux®) used for the treatment of metastatic colorectal cancer that is K-Ras wild-type, EGFR-expressing:
  • In combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) as first-line treatment
  • In combination with irinotecan in individuals who are refractory to irinotecan-based chemotherapy (i.e., the tumor response rate was poor/progression was not halted).
  • As a single agent in individuals who are intolerant to irinotecan or after failure of both irinotecan-based and oxaliplatin-based chemotherapy (i.e., the tumor response rate was poor/progression was not halted).

Colon Cancer
  • Cetuximab (Erbitux®) used in combination with FOLFIRI (infusional fluorouracil, leucovorin, irinotecan) or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimens for the following for left-sided only tumors that express the KRAS/NRAS/BRAF wild-type gene:
    • As primary therapy for locally unresectable or medically inoperable disease
    • For unresectable synchronous liver and/or lung metastases that remain unresectable after primary systemic therapy
    • As primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals with imminent or existing obstruction
    • For unresectable synchronous metastases of other sites
    • As primary treatment for unresectable metachronous metastases in individuals who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months, who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy, or who have not received any previous chemotherapy
    • For unresectable metachronous metastases that remain unresectable after primary treatment
  • Cetuximab (Erbitux®) used as primary treatment for unresectable synchronous liver and/or lung metastases (KRAS/NRAS/BRAF wild-type gene and left-sided tumors only) in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimen FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen.
  • Cetuximab (Erbitux®) used in combination with irinotecan or FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) as primary treatment in individuals with unresectable metachronous metastases (KRAS/NRAS/BRAF wild-type gene and left-sided tumors only) and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months
  • Cetuximab (Erbitux®) used as primary treatment in combination with irinotecan and vemurafenib for individuals with unresectable metachronous metastases (BRAF V600E mutation positive) and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months
  • Cetuximab (Erbitux®) for the subsequent treatment of tumors that express the KRAS/NRAS/BRAF wild-type gene in individuals who have unresectable advanced or metastatic disease and have not previously received cetuximab or panitumumab when administered:
    • In combination with irinotecan or with FOLFIRI (infusional fluorouracil, leucovorin, irinotecan) after the first progression in individuals who previously received oxaliplatin-based regimens without irinotecan
    • in combination with irinotecan or FOLFOX (fluorouracil, leucovorin, and irinotecan) regimen if previously treated with irinotecan-based therapy without oxaliplatin
    • In combination with irinotecan
      • in individuals previously treated with FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen
      • in individuals previously treated with a fluoropyrimidine without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab
  • Cetuximab (Erbitux®) for subsequent therapy in combination with irinotecan and vemurafenib for progression of unresectable advanced or metastatic disease (BRAF V600E mutation positive) not previously treated with cetuximab or panitumumab, in individuals previously treated with:
    • oxaliplatin-based therapy without irinotecan
    • irinotecan-based therapy without oxaliplatin
    • FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen
    • a fluoropyrimidine without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab
  • Cetuximab (Erbitux®) for subsequent therapy in combination with dabrafenib and trametinib or with encorafenib and binimetinib for progression of unresectable advanced or metastatic disease (BRAF V600E mutation positive) not previously treated with cetuximab or panitumumab, in individuals previously treated with:
    • oxaliplatin-based therapy without irinotecan
    • irinotecan-based therapy without oxaliplatin
    • FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen
    • a fluoropyrimidine without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab

Rectal Cancer
  • Cetuximab (Erbitux®) used in combination with FOLFIRI (infusional fluorouracil, leucovorin, irinotecan) or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimens for the following for tumors that express the KRAS/NRAS/BRAF wild-type gene:
    • As primary treatment for T3, N Any; T1-2, N1-2; T4, N Any; or locally unresectable or medically inoperable disease if resection is contraindicated following neoadjuvant therapy
    • For synchronous liver only and/or lung only metastases that are unresectable or medically inoperable and remain unresectable (with no progression of primary tumor) after primary systemic therapy
    • Following short-course radiation therapy (RT) or chemo/RT for synchronous liver only and/or lung only metastases that are unresectable or medically inoperable and remain unresectable (with progression of primary tumor) after primary systemic therapy
    • As primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for patients with existing or imminent obstruction
    • As primary treatment for synchronous unresectable metastases of other sites
    • As primary treatment for unresectable metachronous metastases in patients who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months, who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy, or who have not received any previous chemotherapy
    • For unresectable metachronous metastases that remain unresectable after primary treatment
  • Cetuximab (Erbitux®) for the primary treatment of synchronous liver only and/or lung only metastases (KRAS/NRAS/BRAF wild-type gene only) that are unresectable or medically inoperable, in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimen
  • Cetuximab (Erbitux®) used in combination with irinotecan or FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen in individuals with unresectable metachronous metastases and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months for tumors that express the KRAS/NRAS/BRAF wild-type gene.
  • Cetuximab (Erbitux®) used in combination with irinotecan and vemurafenib for individuals with unresectable metachronous metastases (BRAF V600E mutation positive) and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months
  • Cetuximab (Erbitux®) as subsequent therapy for progression of unresectable advanced or metastatic disease (KRAS/NRAS/BRAF wild-type gene only) not previously treated with cetuximab or panitumumab
    • in combination with irinotecan or with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen if previously treated with oxaliplatin-based therapy without irinotecan
    • in combination with irinotecan or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimen if previously treated with irinotecan-based therapy without oxaliplatin
    • in combination with irinotecan if previously treated with FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen
    • in combination with irinotecan if previously treated with a fluoropyrimidine without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab
  • Cetuximab (Erbitux®) as subsequent therapy in combination with irinotecan and vemurafenib for progression of unresectable advanced or metastatic disease (BRAF V600E mutation positive) not previously treated with cetuximab or panitumumab, in individuals previously treated with:
    • oxaliplatin-based therapy without irinotecan
    • irinotecan-based therapy without oxaliplatin
    • FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen
    • a fluoropyrimidine without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab
  • Cetuximab (Erbitux®) as subsequent therapy in combination with dabrafenib and trametinib or with encorafenib and binimetinib for progression of unresectable advanced or metastatic disease (BRAF V600E mutation positive) not previously treated with cetuximab or panitumumab, in individuals previously treated with:
    • oxaliplatin-based therapy without irinotecan
    • irinotecan-based therapy without oxaliplatin
    • FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen
    • a fluoropyrimidine without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab

Exclusion Criteria
  • Colorectal cancer with any known KRAS or NRAS mutation (mutated or abnormal KRAS/NRAS gene).
  • In individuals with mCRC with disease progression on panitumumab.
  • When cetuximab (Erbitux®) is used as initial therapy, it should not be used in second or subsequent lines of therapy.

HEAD AND NECK CANCER
Cetuximab (Erbitux®) for the treatment of head and neck cancer is considered medically necessary and, therefore, covered when the dosing and frequency requirements listed in Attachment A and the following indications are met:
  • Cetuximab (Erbitux®) used in combination with radiation therapy is indicated for the initial treatment of locally or regionally advanced squamous cell cancer of the head and neck.
  • Cetuximab (Erbitux®) used in combination with platinum-based therapy with 5-FU is indicated for the first-line treatment of recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck.
  • Cetuximab (Erbitux®) administered as a single agent is indicated for the treatment of recurrent or metastatic squamous cell cancer of the head and neck in individuals who previously failed or are refractory to platinum-based chemotherapy.
  • Cetuximab (Erbitux®) administered as a single agent is indicated for the treatment of non-nasopharyngeal cancer with sequential chemoradiation following induction chemotherapy for the following:
    • Individuals who have newly diagnosed T4b, N0-3, M0 disease, unresectable nodal disease with no metastases, who are unfit for surgery, or unresectable locoregional recurrence and who have not received prior radiation therapy with performance status (PS) 0-1.
    • Individuals with resectable locoregional recurrence and who have not received prior radiation therapy.
  • Cetuximab (Erbitux®) is indicated for the systemic first-line, second-line, or subsequent treatment of non-nasopharyngeal cancer as a single agent for individuals with newly diagnosed T4b, N0-3, M0 disease, unresectable nodal disease with no metastases, unresectable locoregional recurrence and no prior radiation therapy (RT), or for individuals who are unfit for surgery and performance status (PS) 3.
  • Cetuximab (Erbitux®) is indicated as systemic first-line, second-line, or subsequent treatment as a single agent (non-nasopharyngeal cancer) in PS 0-2 individuals or in combination (PS 0-1) with carboplatin (nasopharyngeal cancer) or cisplatin (non-nasopharygeal cancer) alone, or in combination with cisplatin or carboplatin and either fluorouracil (both NCCN-preferred regimens), docetaxel, or paclitaxel (non-nasopharyngeal cancer) for metastatic (M1) disease at initial presentation, recurrent/persistent disease with distant metastases, or unresectable locoregional recurrence or second primary with prior RT.
  • Cetuximab (Erbitux®) administered as a single agent is indicated for the treatment of cancer of the glottic larynx with T3, N0-3 disease requiring (amenable to) total laryngectomy (consider for selected individuals with T4a who decline surgery) with primary concurrent chemoradiation
  • Cetuximab (Erbitux®) administered as a single agent is indicated for the treatment of cancer of the hypopharynx
    • With primary concurrent chemoradiation for T1, N+
    • With primary concurrent chemoradiation for T2-3, N0-3 disease requiring (amenable to) pharyngectomy with partial or total laryngectomy
    • As sequential chemoradiation for T4a, N0-3 disease with partial response at the primary site and stable or improved disease in the neck following induction chemotherapy (consider for selected individuals with T4a, N0-3 following a complete response at the primary site and stable or improved disease in the neck following induction chemotherapy)
  • Cetuximab (Erbitux®) used in combination with carboplatin is indicated as primary therapy for the treatment of T1-4, N0-3, M1 cancer of the nasopharynx.
  • Cetuximab (Erbitux®) administered as a single agent is indicated for the treatment of cancer of the oropharynx for the following:
    • With primary concurrent or sequential chemoradiation for either p16-negative T3-4a, N0-1 disease, or p16-negative T1-4, N2-3 disease
    • With primary concurrent or sequential chemoradiation for one of the following p16 (HPV)-positive disease:
      • T1-2, N1 (single node >3 cm, or 2 or more ipsilateral nodes ≤6 cm), T1-2, N2 or T3, N0-2 disease
      • T1-3, N3 or T4, N0-3 disease (as an NCCN-preferred regimen for primary concurrent chemoradiation)
  • Cetuximab (Erbitux®) administered for initial definitive treatment for occult primary with sequential chemoradiation following induction chemotherapy for N2-3 disease.

NON-MELANOMA SKIN CANCERS
Cetuximab (Erbitux®) for the treatment of squamous cell skin cancer for inoperable positive regional lymph nodes, regional recurrence, or distant metastases is considered medically necessary and, therefore, covered when the dosing and frequency requirements listed in Attachment A are met.

PENILE CANCER
Cetuximab (Erbitux®) for the treatment of penile cancer is considered medically necessary and, therefore, covered when used as a single agent therapy for subsequent-line systemic treatment of metastatic disease and the dosing and frequency requirements listed in Attachment A are met.

NON-SMALL CELL LUNG CANCER (NSCLC)
Cetuximab (Erbitux®) for the treatment of non-small cell lung cancer is considered medically necessary and, therefore, covered when the dosing and frequency requirements listed in Attachment A and the following indications are met:
  • In combination with afatinib as subsequent therapy for recurrent, advanced or metastatic disease in individuals with a known sensitizing EGFR mutation:
    • who have progressed on EGFR tyrosine kinase inhibitor therapy for asymptomatic disease, symptomatic brain lesions, or isolated symptomatic systemic lesions.
    • who are T790M negative, have progressed on EGFR tyrosine kinase inhibitor therapy, and have multiple symptomatic systemic lesions.

EXPERIMENTAL/INVESTIGATIONAL

All other uses of cetuximab (Erbitux®) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

DOSING AND FREQUENCY REQUIREMENTS

Refer to Attachment A for dosing and frequency requirements for cetuximab (Erbitux®).

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this Policy to ensure consistency with the most recently published recommendations for the use of cetuximab (Erbitux®). Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of cetuximab (Erbitux®) outside of the Dosing and Frequency Requirements listed in this Policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for cetuximab (Erbitux®).

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

When coverage of cetuximab (Erbitux®) is requested outside of the Dosing and Frequency Guidelines listed in this Policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.
Policy Guidelines

There is no Medicare coverage determination addressing this service; therefore, the Company policy is applicable.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, cetuximab (Erbitux®) may be covered under the medical benefits of the Company’s Medicare Advantage products when medical necessity criteria and dosing and frequency requirements listed in this medical policy are met.

Cetuximab (Erbitux®) may be available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when cetuximab (Erbitux®) is covered under a member's medical benefit. It does not address instances when cetuximab (Erbitux®) is covered under a member’s pharmacy benefit.

DRUG ADMINISTRATION

Cetuximab (Erbitux®) is administered by intravenous (IV) infusion and should not be given as an IV push or bolus.

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

The ECOG has developed the ECOG Performance Status; it was originally published in 1982 in the American Journal of Clinical Oncology*. ECOG states, "These scales and criteria are used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. They are included here for health care professionals to access."

ECOG Performance Status
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2
Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50 percent of waking hours
3
Capable of only limited self care, confined to bed or chair more than 50 percent of waking hours
4
Completely disabled. Cannot carry on any self care: Totally confined to bed or chair
5
Dead
*Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

The FDA's approval of cetuximab (Erbitux®) was initially issued on February 12, 2004. Supplemental approvals have since been issued. The safety and effectiveness of cetuximab (Erbitux®) in pediatric individuals have not been established.

Description

Cetuximab (Erbitux®) is a recombinant monoclonal antibody and an antineoplastic agent that works differently than standard chemotherapy or hormonal therapy. It also has been shown to enhance the antitumor effects of other chemotherapy. Monoclonal antibodies may be used to target and destroy certain cancer cells while causing little harm to normal cells. Cetuximab (Erbitux®) binds to the extracellular domain of the human epidermal growth factor receptor (EGFR), which is expressed in many human cancers, including head and neck cancer and colon and rectum cancer. Cetuximab (Erbitux®), by attaching itself to the EGFR of cancer cells, is able to prevent the receptors from being activated. Through various mechanisms, it is able to inhibit cell division, promote cell death, and inhibit angiogenesis and metastasis.

METASTATIC COLORECTAL CANCER

The US Food and Drug Administration (FDA) has issued several approvals for its use in metastatic colorectal cancer (mCRC). Cetuximab (Erbitux®) received initial FDA approval in 2004 for the treatment of EGFR-expressing metastatic colorectal cancer (mCRC) either in combination with irinotecan or as a single agent, when there is an intolerance to irinotecan. An FDA approval in 2008 expanded the use of cetuximab (Erbitux®) as a single agent in mCRC after failure of both irinotecan-based and oxaliplatin-based chemotherapy. A more recent FDA approval, in 2012, allows for the use of cetuximab (Erbitux®) in combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for first-line treatment of mCRC.

Cetuximab (Erbitux®) therapy in mCRC is further guided by the status of the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene and neuroblastoma RAS (NRAS) gene. When KRAS or NRAS mutations exist, the genes are said to be abnormal or mutated. When no mutations exist, KRAS/NRAS are said to be normal or wild-type (non-mutated). Clinical trial data show that patients with KRAS/NRAS-mutated mCRC do not benefit from cetuximab. An FDA-approved test has been developed to determine the KRAS/NRAS mutation status of mCRC. The FDA, in addition to NCCN, warns that analysis should be performed "in laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance can lead to unreliable test results."

The NCCN compendium notes when cetuximab (Erbitux®) is used as initial therapy, it should not be used in second or subsequent lines of therapy for colorectal cancer. In addition, Cetuximab (Erbitux®) is not recommended in individuals with mCRC with disease progression on panitumumab.

HEAD AND NECK CANCERS
In 2006, the FDA issued a supplemental approval for the use of cetuximab (Erbitux®) in certain types of locally or regionally advanced, recurrent, or metastatic squamous cell head and neck cancers, either as a single agent or in combination with radiation therapy. In 2011, cetuximab (Erbitux®) was indicated for use in combination with platinum-based therapy with 5-FU for the first-line treatment of recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References

Allegra CJ, Jessup JM, Somerfield MR, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti–epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009;27(12):2091-2096.

Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(10):1626-34.

American Society of Clinical Oncology (ASCO). 2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer. J Oncol Pract. 2012;8(1):63-6.

Azzoli CG, Baker S Jr, Temin S, et al. American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non–small-cell lung cancer. J Clin Oncol.2009;27(36):6251-6266.

Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, et al. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res. 2007;67(6):2643-8.

Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center. KRAS mutations and epidermal growth factor receptor inhibitor therapy in metastatic colorectal cancer. [technology assessment]. Assessment Program Volume 23, No. 6. January 2009.

Bokemeyer C, Bondarenko I, Hartmann JT, et al. KRAS status and efficacy of first-line treatment of patients with metastatic colorectal (mCRC) with FOLFOX with or without cetuximab: The OPUS experience. J Clin Oncol. 2008;26(15 suppl):abstract 4000.

Cetuximab. American Hospital Formulary Service (AHFS). AHFS Drug Information 2019. [Lexicomp Online Web site]. 04/28/2015. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed September 9, 2019.

Cetuximab (Erbitux®). Elsevier's Clinical Pharmacology Compendium. [ClinicalKey Web site]. 06/24/2019. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed September 9, 2019.

Cetuximab (Erbitux®). Lexi-Drugs Compendium. [Lexicomp Online Web site]. 08/21/2019. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed September 9, 2019.

Cetuximab. Truven Health Analytics. Micromedex® DrugDex® Compendium. Greenwood Village, CO. [Micromedex® Solutions Web site]. Last modified: 05/08/2019. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed September 9, 2019.

De Roock W, Piessevaux H, De Schutter J, et al. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol. 2008;19(3):508-15.

Di Fiore F, Blanchard F, Charbonnier F, et al. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy. Br J Cancer. 2007;96(8):1166-9.

ECOG-ACRIN Cancer Research Group. ECOG performance status. [ECOG Web site]. Available at: http://ecog-acrin.org/resources/ecog-performance-status. Accessed September 5, 2019.

Erbitux® (cetuximab) [prescribing information]. 04/2019. ImClone Systems Incorporated, Eli Lilly and Company. Available at: https://www.erbitux.com/hcp/?utm_id=bi_cmp-291515677_adg-1268836665642936_ad-79302335652989_kwd-79302450469161:loc-190_dev-c_ext-&utm_source=bing&utm_medium=cpc&utm_campaign=US_HCP_Erbitux_Brand_Alone%20-%20Partners%20-%202017&utm_term=erbitux&utm_content=Alone%20-%20EX . Accessed September 5, 2019.

Helwick C. Cetuximab confers survival benefit in all-RAS wild-type colorectal tumors. The ASCO Post. December 1, 2013;4(19). Available at: http://www.ascopost.com/issues/december-1,-2013/cetuximab-confers-survival-benefit-in-all-ras-wild-type-colorectal-tumors.aspx. Accessed September 9, 2019.

Helwick C. Time to think beyond KRAS in metastatic colorectal cancer. The ASCO Post. December 1, 2013;4(19). Available at: http://www.ascopost.com/issues/december-1,-2013/time-to-think-beyond-kras-in-metastatic-colorectal-cancer.aspx. Accessed September 9, 2019.

Khambata-Ford S, Garrett CR, Meropol NJ, et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol. 2007;25(22):3230-7.

Lievre A, Bachet JB, Boige V, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008;26(3):374-9.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Cetuximab (Erbitux®). [NCCN Web site]. 2019. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/PrintMatrix.aspx?AID=5 [via subscription only]. Accessed September 5, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Non-small cell lung cancer.Version 7.2019. [NCCN Web site]. 08/30/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed September 9, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Colon Cancer. Version 2.2019. Updated 05/15/2019. Available at: http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed September 9, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Head and Neck Cancers. Version 2.2019. updated 06/28/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf . Accessed September 9, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Penile Cancer. Version 2.2019. updated 05/13/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/penile.pdf. Accessed September 5, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Rectal Cancer. Version 2.2019. updated 05/15/2019. Available at: http://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf. Accessed September 9, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Squamous Cell Skin Cancer. Version 2.2019. updated 10/23/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. Accessed September 9, 2019.

Novitas Solutions, Inc. Local Coverage determination (LCD). LCD L35396: Biomarkers for Oncology. [Novitas Solutions, Inc. Medicare Services Web site]. Original: 10/01/2015 (Revised: 06/13/2019). Available at: https://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=35396 . Accessed September 5, 2019.

Punt CJ, Tol J, Rodenburg CJ, et al. Randomized phase III study of capecitabine, oxaliplatin, and bevacizumab with or without cetuximab in advanced colorectal cancer (ACC), the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). J Clin Oncol. 2008; 26(15 suppl);abstract LBA4011.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Labeling for Erbitux® (cetuximab). [FDA Web site]. 04/2019. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed September 5, 2019.

Van Cutsem E, Lang I, D’haens G, et al. KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: The CRYSTAL experience. J Clin Oncol. 2008;26(15 suppl):abstract 2.

Van Cutsem E, Nowacki M, Lang I, et al. Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial. J Clin Oncol. 2007;25(18 suppl):abstract 4000.

Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007;25(13):1658-64.


Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See Attachment B


HCPCS Level II Code Number(s)

J9055: Injection, cetuximab, 10 mg


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References

Attachment A: Cetuximab (Erbitux®)
Description: Dosing and Frequency Requirements

Attachment B: Cetuximab (Erbitux®)
Description: ICD-10 Codes for Cetuximab (Erbitux®)







Policy History

Revisions from MA08.031d
12/02/2019This policy has been updated to communicate the coverage criteria for cetuximab (Erbitux®), in accordance with the US Food and Drug Administration (FDA) prescribing information and the National Comprehensive Cancer Network (NCCN) Compendia. Revisions have been made to all conditions, including Dosing and Frequency Requirements.

Revisions from MA08.031c
10/01/2018This policy has been identified for the ICD-10 CM code update, effective 10/01/2018.

The following CD-10 CM codes have been termed from this policy:
C44.122 Squamous cell carcinoma of skin of right eyelid, including canthus
C44.129 Squamous cell carcinoma of skin of left eyelid, including canthus

The following ICD-10 CM codes have been added to the attachment B:
C44.1221 Squamous cell carcinoma of skin of right upper eyelid, including canthus
C44.1222 Squamous cell carcinoma of skin of right lower eyelid, including canthus
C44.1291 Squamous cell carcinoma of skin of left upper eyelid, including canthus
C44.1292 Squamous cell carcinoma of skin of left lower eyelid, including canthus



Revisions from MA08.031b
06/14/2017This version of the policy will become effective 06/14/2017.

This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and NCCN compendia.

Coverage was added for the condition of non-small cell lung cancer with criteria. Criteria were updated for the conditions of colon cancer, rectal cancer, and head and neck cancers.

The following ICD-10 CM codes have been added to Attachment B in this policy:
C34.10, C34.11, C34.12, C34.2, C34.30, C34.31, C34.32, C34.80, C34.81, C34.82, C34.90, C34.91, C34.92, C63.8

The following ICD-10 CM codes have been removed from Attachment B in this policy:
C00.0, C00.1, C00.2, C00.3, C00.4, C00.5, C00.6, C00.8, C00.9, C07, C08.0, C08.1, C08.9, C21.0, C21.1, C21.2, C31.0, C31.1, C31.2, C31.3, C31.8, C31.9, C44.02, C76.0, C78.30, C78.39, C78.5, C78.6, C80.1, Z85.038, Z85.048, Z85.21, Z85.22, Z85.810, Z85.818, Z85.819


Revisions from MA08.031a
11/23/2016This policy has been reissued in accordance with the Company’s annual review process.
12/02/2015This version of the policy will become effective 12/02/2015.

This policy was updated to be consistent with the indications and dosing/frequency outlined in the National Comprehensive Cancer Network (NCCN) compendium.

The following ICD-10 CM codes have been added to Attachment B in this policy: C60.0, C60.1, C60.2, C60.8,
C60.9.

The following ICD-10 CM codes have been removed from Attachment B in this policy: C33, C34.00, C34.01,
C34.02, C34.10, C34.11, C34.12, C34.2, C34.30, C34.31, C34.32, C34.80, C34.81, C34.82, C34.90, C34.91,
C34.92, C79.2, C79.89, C79.9.


Revisions from ma08.031
01/01/2015This is a new policy.




Version Effective Date: 12/02/2019
Version Issued Date: 12/02/2019
Version Reissued Date: N/A