66733-0948-XX Erbitux 100 MG/50ML SOLN (LILLY)
66733-0958-XX Erbitux 200 MG/100ML SOLN (LILLY)
Cetuximab is a recombinant human/mouse chimeric monoclonal antibody that binds specifically to the extracellular domain of the human epidermal growth factor receptor (EGFR). EGFR is a transmembrane glycoprotein expressed in multiple normal epithelial tissues and in many human cancers. By binding to the EGFR, cetuximab competitively inhibits the binding of natural ligands, including epidermal growth factor (EGF). This blocks the complex downstream signaling of the EGFR cascade and results in inhibition of cell growth, induction of apoptosis and decreased production of matrix metalloproteinase and vascular endothelial growth factor (VEGF).
In the EGFR cascade, RAS proteins, including KRAS, normally function as switches in the kinase pathway activated between cell surface EGFR and downstream signaling. Mutations in the KRAS gene, occurring in 30% to 50% of colorectal cancers and common in other tumor types, activate the EGFR pathway and bypass the need for ligand binding. This renders cetuximab and other anti-EGFR agents ineffective against those tumors expressing RAS mutations such as KRAS and, found more recently, those in another of the RAS proteins, NRAS.
Another common mutation is found in the BRAF gene, a serine/threonine kinase. BRAF encodes a component downstream of the RAS proteins in the EGFR cascade. The BRAF gene is important for transducing mitogenic signals from the cell surface. BRAF mutations have been found in thyroid, colorectal and lung cancers as well as in a majority of malignant melanomas, however specific targeting and treatment of BRAF-dependent tumors remains under investigation.
Cetuximab for the treatment of the following is considered medically necessary if the medical appropriateness criteria are met: (See Medical Appropriateness below.)
Head and Neck Cancer
Non-Melanoma Skin Cancer
Non-Small Cell Lung Cancer
Cetuximab for the treatment of other conditions/diseases is considered investigational.
Testing for mutation of the BRAF gene in the use of cetuximab is considered investigational.
Cetuximab is considered medically appropriate if ALL of the following:
Individual is 18 years of age or older
Diagnosis of ANY ONE of the following:
Colorectal Cancer (CRC) if ALL of the following:
KRAS and NRAS genes are normal (e.g., without mutation, wild type) as determined by FDA-approved tests (http://www.fda.gov/companiondiagnostics)
Will NOT be used as part of an adjuvant treatment regimen
Individual has NOT been previously treated with cetuximab or panitumumab
Individual has progressive, metastatic or unresectable advanced disease with ANY ONE of the following:
Previous failure on an oxaliplatin- and irinotecan-based regimen
Inability to tolerate irinotecan
Used as ANY ONE of the following:
Single agent therapy for metastatic disease
First-line or primary therapy for left-sided tumors only (unless restricted to rectal involvement) in combination with ANY ONE of the following:
Irinotecan after previous adjuvant FOLFOX or CapeOX within the past 12 months
Subsequent therapy in combination with irinotecan or irinotecan-based therapy for refractory disease or in combination with FOLFOX regimen if previously treated with irinotecan-based therapy without oxaliplatin
Used in combination with vemurafenib and irinotecan in individuals with BRAF V600E mutation positive disease as ANY ONE of the following:
Primary therapy after previous adjuvant FOLFOX or CapeOX within the past 12 months
Subsequent therapy for disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, or irinotecan-based therapy
Subsequent therapy in combination with dabrafenib and trametinib or with encorafenib and binimetinib in patients with BRAF V600E mutation positive disease for disease progression after previous treatment with fluoropyrimidine-, oxaliplatin-, or irinotecan-based therapy
Head and Neck Cancer that is squamous cell carcinoma (SCCHN) and ALL of the following:
Used in ANY ONE of the following types:
Cancer of the Glottic Larynx
Cancer of the Hypopharynx
Cancer of the Nasopharynx
Cancer of the Oropharynx
Cancer of the Supraglottic Larynx
Occult Primary Head and Neck Cancer only in initial treatment as a single agent with sequential chemoradiation following induction chemotherapy
Very Advanced Head and Neck Cancer
Treatment is ANY ONE of the following:
Locally or regionally advanced squamous cell carcinoma of the head and neck for first-line treatment in combination with radiation therapy
As a single agent in recurrent or metastatic disease after failure on platinum-based therapy
In combination with platinum-based therapy for first-line treatment of recurrent, loco-regional, or metastatic disease
As a single-agent with or without sequential chemoradiation, or in combination with chemotherapy
Non-Melanoma Skin Cancer if ALL of the following:
Diagnosis is squamous cell skin cancer
Disease is regional recurrence, inoperable positive regional lymph nodes or distant metastases
Non-Small Cell Lung Cancer (NSCLC) that is ALL of the following:
Recurrent, advanced or metastatic disease (excluding locoregional recurrence or symptomatic local disease)
Used in combination with afatinib
Subsequent therapy for sensitizing EGFR mutation-positive tumors
Individual has progressed on EGFR tyrosine kinase inhibitor therapy (e.g., afatinib, gefitinib or erlotinib) with ANY ONE of the following:
Has asymptomatic disease, symptomatic brain lesions, or isolated symptomatic systemic lesions
Is T790M mutation negative with multiple symptomatic systemic lesions
Penile Cancer for use as single agent treatment for subsequent therapy of metastatic disease
Cetuximab is considered medically appropriate for renewal if ALL of the following criteria are met:
Individual continues to meet approval criteria
Tumor response is indicated by stabilization of disease or decrease in tumor size or tumor spread
Absence of unacceptable toxicity from the drug, e.g., severe infusion reactions cardiopulmonary arrest, pulmonary toxicity/interstitial lung disease, dermatologic toxicity, hypomagnesemia/electrolyte abnormalities, etc.
DOSAGE & ADMINISTRATION
400 mg/m² loading dose; then 250 mg/m² every 7 days until disease progression or unacceptable toxicity;
OR500 mg/m² every 14 days until disease progression or unacceptable toxicity
All other indications
400mg/m² loading dose; then 250mg/m² every 7 days until disease progression or unacceptable toxicity
LENGTH OF AUTHORIZATION
Coverage will be provided for six months and may be renewed
Refer to DOSAGE LIMITS below
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).
Allegra, C. J., Rumble, R. B., Hamilton, S. R., Mangu, P. B., Roach, N., Hantel, A., et al. (2016). Extended RAS gene mutation testing in metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy: American Society of Clinical Oncology provisional clinical opinion update 2015. Journal of Clinical Oncology. 34 (2), 179-185.
Lexi-Comp Online. (2019). AHFS DI. Cetuximab. Retrieved July 1, 2019 from Lexi-Comp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2019, May). Cetuximab. Retrieved July 1, 2019 from MICROMEDEX Healthcare Series.
National Comprehensive Cancer Network. (2019). NCCN Drugs & Biologics Compendium®. Cetuximab. Retrieved March 13, 2019 from National Comprehensive Cancer Network.
U. S. Food and Drug Administration. (2019, April). Center for Drug Evaluation and Research. Erbitux® (Cetuximab) injection, for intravenous use. Retrieved July 1, 2019 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125084s273lbl.pdf.
ORIGINAL EFFECTIVE DATE: 3/10/2005
MOST RECENT REVIEW DATE: 10/31/2019
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
This document has been classified as public information.
Maximum billable units per dose and over time by indication as a Medical Benefit; 1 billable unit = 10 mg