BlueCross BlueShield of Tennessee Medical Policy Manual

Cetuximab (Erbitux®)

NDC CODE(S)

66733-0948-XX ERBITUX 100MG/50ML Solution (ELI LILLY & CO.)

66733-0958-XX ERBITUX 2MG/ML Solution (ELI LILLY & CO.)

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.

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL CRITERIA

Colorectal Cancer (CRC)

Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Occult Primary Head and Neck Cancers

Squamous Cell Skin Cancer

Penile Cancer

Non-Small Cell Lung Cancer (NSCLC)

*If confirmed using an FDA approved assay - http://www.fda.gov/companiondiagnostics

RENEWAL CRITERIA

DOSAGE/ADMINISTRATION

INDICATION

DOSE

Colorectal Cancer

400 mg/m² loading dose intravenously, then 250 mg/m² intravenously every 7 days until disease progression or unacceptable toxicity; OR

500 mg/m² intravenously every 14 days until disease progression or unacceptable toxicity

NSCLC

500 mg/m² intravenously every 14 days until disease progression or unacceptable toxicity

SCCHN

In combination with radiation therapy:

400 mg/m² loading dose, then 250 mg/m² every 7 days for the duration of radiation therapy (6-7 weeks)

Monotherapy or in combination with platinum-based therapy:

400 mg/m² loading dose, then 250 mg/m² every 7 days until disease progression or

unacceptable toxicity

All other indications

400 mg/m² loading dose, then 250 mg/m² every 7 days until disease progression or

unacceptable toxicity

LENGTH OF AUTHORIZATION

Coverage will be provided for six months and may be renewed unless otherwise specified.

 

DOSAGE LIMITS

Max Units (per dose and over time) [HCPCS Unit]:

Weekly

Every two weeks

-  Load: 100 billable units x 1 dose

-  Maintenance Dose: 60 billable units every 7 days

120 billable units every 14 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).

SOURCES

1.     Erbitux [package insert]. Branchburg, NJ; ImClone LLC; November 2020; Accessed January 2021.

2.     Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) cetuximab. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

3.     Bouchahda M, Macarulla G, Lledo F, et al. Efficacy and safety of cetuximab (C) given with a simplified, every other week (q2w), schedule in patients (pts) with advanced colorectal cancer (aCRC): a multicenter, retrospective study. J Clin Oncol. 2008; 26(15S): Abstract 15118. Presented at: The 44th American Society of Clinical Oncology Annual Meeting (ASCO). May 30–June 3, 2008. Chicago, Illinois.

4.     Mrabti H, La Fouchardiere C, Desseigne F, Dussart S, Negrier S, Errihani H. Irinotecan associated with cetuximab given every 2 weeks versus cetuximab weekly in metastatic colorectal cancer. J Can Res Ther. 2009; 5:272-6.

5.     Shitara K, Yuki S, Yoshida M, et al. Phase II study of combination chemotherapy with biweekly cetuximab and irinotecan for wild-type KRAS metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines World J Gastroenterol, 2011, April 14; 17(14): 1879-1888

6.     Pfeiffer P, Bjerregarrd JK, Qvortrup C, et al, Simplification of Cetuximab (Cet) Administration: Double Dose Every Second Week as a 60 Minute Infusion. J Clin Oncol, 2007, 25(18S):4133 [abstract 4133 from 2007 ASCO Annual Meeting Proceedings, Part I].

7.     Pfeiffer P, Nielsen D, Bjerregaard J, et al, “Biweekly Cetuximab and Irinotecan as Third-Line Therapy in Patients with Advanced Colorectal Cancer after Failure to Irinotecan, Oxaliplatin and 5-Fluorouracil,” Ann Oncol, 2008, 19(6):1141-5.

8.     Carneiro BA, Ramanathan RK, Fakih MG, et al. Phase II study of irinotecan and cetuximab given every 2 weeks as second-line therapy for advanced colorectal cancer. Clin Colorectal Cancer. 2012 Mar; 11(1):53-9.

9.     Fahrenbruch R, Kintzel P, Bott AM, et al. Dose Rounding of Biologic and Cytotoxic Anticancer Agents: A Position Statement of the Hematology/Oncology Pharmacy Association. J Oncol Pract. 2018 Mar;14(3):e130-e136.

10.  Hematology/Oncology Pharmacy Association (2019). Intravenous Cancer Drug Waste Issue Brief. Retrieved from http://www.hoparx.org/images/hopa/advocacy/Issue- Briefs/Drug_Waste_2019.pdf

11.  Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788

12.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Colon Cancer. Version 1.2021. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

13.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Rectal Cancer. Version 1.2021. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

14.  Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78.

15.  Vermrorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. doi: 10.1056/NEJMoa0802656.

16.  Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol. 2007 Jun 1;25(16):2171-7.

17.  Van Cutsem E, Köhne CH, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. doi: 10.1056/NEJMoa0805019.

18.  Jonker DJ, O'Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007 Nov 15;357(20):2040-8.

19.  Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):337-45.

20.  Samstein RM, Ho AL, Lee NY, et al. Locally advanced and unresectable cutaneous squamous cell carcinoma: outcomes of concurrent cetuximab and radiotherapy. J Skin Cancer. 2014;2014:284582. doi: 10.1155/2014/284582. Epub 2014 Jul 21.

21.  Maubec E, Petrow P, Scheer-Senyarich I, et al. Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable squamous cell carcinoma of the skin. J Clin Oncol. 2011 Sep 1;29(25):3419-26. doi: 10.1200/JCO.2010.34.1735. Epub 2011 Aug 1.

22.  Carthon BC, Ng CS, Pettaway CA, et al. Epidermal growth factor receptor-targeted therapy in locally advanced or metastatic squamous cell carcinoma of the penis. BJU Int. 2014 Jun;113(6):871-7. doi: 10.1111/bju.12450.

23.  Janjigian YY, Smit EF, Groen HJ, et al. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014 Sep;4(9):1036-45. doi: 10.1158/2159-8290.CD-14-0326. Epub 2014 Jul 29.

24.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Non-Small Cell Lung Cancer. Version 2.2021. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

25.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Head and Neck Cancers. Version 1.2021. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

26.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Penile Cancer. Version 2.2020. National Comprehensive Cancer Network, 2020. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

27.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Squamous Cell Skin Cancer. Version 2.2020. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

28.  Lexi-Comp Online. (February 2021). AHFS DI. Cetuximab. Retrieved March 23, 2021 from Lexi-Comp Online with AHFS.

29.  MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2021, March). Cetuximab. Retrieved March 23, 2021 from MICROMEDEX Healthcare Series.

ORIGINAL EFFECTIVE DATE:  3/10/2005

MOST RECENT REVIEW DATE:    7/31/2021

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.

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