BlueCross BlueShield of Tennessee Medical Policy Manual

Cetuximab

NDC CODE(S)

66733-0948-xx Erbitux 100 MG/50ML SOLN (LILLY)

 

66733-0958-xx Erbitux 200 MG/100ML SOLN (LILLY)

DESCRIPTION

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.

REFER TO DECISION SUPPORT TREE

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL

RENEWAL CRITERIA
INDICATION(S) DOSAGE & ADMINISTRATION
Colorectal Cancer

400mg/m² x 1 loading dose then 250mg/m² every 7 days OR

500mg/m² every 14 days
All other indications

400mg/m² x 1 loading dose then 250mg/m² every 7 days

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.

IMPORTANT REMINDER

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.

ADDITIONAL INFORMATION 

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).

No controlled studies were found in the published literature that validate the use of cetuximab for the treatment of other conditions or diseases.

SOURCES

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.

BlueCross BlueShield Association. Medical Policy Reference Manual. (5:2016). KRAS and BRAF mutation analysis in metastatic colorectal cancer. (2.04.53). Retrieved April 11, 2017 from BlueWeb.

Lexi-Comp Online. (2017, March). AHFS DI. Cetuximab. Retrieved April 6, 2017 from Lexi-Comp Online with AHFS.

MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2017, February). Cetuximab. Retrieved April 6, 2017 from MICROMEDEX Healthcare Series.

National Comprehensive Cancer Network. (2017). NCCN Drugs & Biologics Compendium®. Cetuximab. Retrieved April 6, 2017 from National Comprehensive Cancer Network.

U. S. Food and Drug Administration. (2016, October). Center for Drug Evaluation and Research. Erbitux® (Cetuximab) label. Retrieved April 6, 2017 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125084s265lbl.pdf.

ORIGINAL EFFECTIVE DATE:  3/10/2005

MOST RECENT REVIEW DATE:  6/6/2017

ID_MRx

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.

Pharmaceutical Decision Support Tree

Cetuximab (Erbitux®)

  1. Is this the initial request for the agent?

If yes, go to question #2

If no, go to question #8

  1. Does the individual have a diagnosis of colorectal cancer that is progressive, metastatic or unresectable advanced disease, the KRAS and NRAS genes are normal (e.g., without mutation, wild type) and the request is for use as a single agent or in combination with an irinotecan- or oxaliplatin-based regimen?

If yes, go to question #7

If no, go to question #3

  1. Does the individual have a diagnosis of head and neck cancer that is squamous cell carcinoma (SCCHN) and ANY ONE of the following?

If yes, go to question #7

If no, go to question #4

  1. Does the individual have a diagnosis of non-melanoma skin cancer if ALL of the following?

If yes, go to question #7

If no, go to question #5

  1. Does the individual have a diagnosis of non-small cell lung cancer that is ALL of the following?

If yes, go to question #7

If no, go to question #6

  1. Does the individual have a diagnosis of penile cancer requesting single agent treatment for subsequent therapy of metastatic disease?

If yes, go to question #7

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the request for a loading dose of 100 billable units for one dose and 60 billable units every 7 days or 120 billable units every 14 days or less for dosage of the following for an authorization of 6 months?

Colorectal Cancer

400mg/m² x 1 loading dose then 250mg/m² every 7 days OR

500mg/m² every 14 days
All other indications

400mg/m² x 1 loading dose then 250mg/m² every 7 days

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Does the individual continue to meet the initial approval criteria in questions 2 through 7?

If yes, go to question #9

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is there indication of tumor response with stabilization of disease or decrease in tumor size or tumor spread?

If yes, go to question #10

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is there absence of unacceptable toxicity from the drug, e.g., interstitial lung disease, acneiform rash, skin drying and fissuring, paronychial inflammation, infectious sequelae [for example, S. aureus sepsis, abscess formation, cellulitis, blepharitis, conjunctivitis, keratitis/ulcerative keratitis with decreased visual acuity, cheilitis] and hypertrichosis bullous mucocutaneous disease with blisters, erosions, and skin sloughing?

If yes, this satisfies medical necessity and medical appropriateness criteria for renewal

If no, this does not meet medical necessity and/or medical appropriateness criteria

This document has been classified as public information.