Last Review Date: 12/01/2020

Date of Origin: 12/22/2009

Dates Reviewed: 07/2010, 09/2010, 12/2010, 03/2011, 06/2011, 09/2011, 12/2011, 03/2012, 06/2012, 09/2012, 11/2012, 12/2012, 03/2013, 06/2013, 09/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 05/2015, 08/2015, 11/2015, 02/2016, 05/2016, 08/2016, 11/2016, 02/2017, 05/2017, 08/2017, 11/2017, 02/2018, 05/2018, 09/2018, 12/2018, 03/2019, 06/2019, 09/2019, 12/2019, 03/2020, 06/2020, 09/2020, 12/2020

I. Length of Authorization 

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

• SCCHN in combination with radiation therapy:  Coverage will be provided for the duration of radiation therapy (6-7 weeks).

II. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:
2. Max Units (per dose and over time) [HCPCS Unit]:

III. Initial Approval Criteria 

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Colorectal Cancer (CRC) † 

• Patient is both KRAS and NRAS mutation negative (wild-type) as determined by an FDA-approved or CLIA-compliant test*; AND
• Will not be used as part of an adjuvant treatment regimen; AND
• Patient has not been previously treated with cetuximab or panitumumab; AND
  • Patient has metastatic, unresectable, or advanced disease that is BRAF mutation negative (wild-type); AND
    • Used as first-line or primary therapy; AND
      • Used in combination with FOLFIRI †; OR
      • Used in combination with FOLFOX (Note: For colon cancer patients with left sided tumors only); OR
      • Used in combination with irinotecan after previous adjuvant FOLFOX or CapeOX within the past 12 months (Note: For colon cancer patients with left sided tumors only); OR
    • Used as subsequent therapy; AND
      • Used in combination with irinotecan for oxaliplatin- and/or irinotecan-refractory disease; OR
      • Used in combination with FOLFIRI for oxaliplatin-refractory disease; OR
      • Used in combination with FOLFOX for irinotecan-refractory disease; OR
      • Used as a single agent for oxaliplatin- and irinotecan-refractory disease OR irinotecan-intolerant disease; OR
    • Used in combination with FOLFOX or FOLFIRI for one of the following (Note: For colon cancer patients with left sided tumors only):
      • Unresectable metastatic disease that remains unresectable after primary systemic therapy; OR
      • Unresectable metastatic disease in patients who have received adjuvant FOLFOX or CapeOX more than 12 months ago OR who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy; OR
      • Disease progression on non-intensive therapy with improvement in functional status (excluding patients previously treated with fluoropyrimidine); OR
  • Patient has BRAF V600E mutation positive disease; AND
    • Used in combination with encorafenib; AND
      • Used as subsequent therapy for disease progression after at least one prior line of treatment in the advanced or metastatic disease setting; OR
      • Used as primary treatment for unresectable metastatic disease after previous adjuvant FOLFOX or CapeOX within the past 12 months

Squamous Cell Carcinoma of the Head and Neck (SCCHN) † Ф 

• Used in one of the following regimens: †
  • In combination with radiation therapy for first-line treatment of regionally or locally advanced disease; OR
  • As a single agent in recurrent or metastatic disease after failure on platinum-based therapy; OR
  • In combination with platinum-based therapy for first-line treatment of recurrent locoregional or metastatic disease; AND
• Patient has one of the following sub-types of SCCHN: ‡
  • Cancer of the Glottic Larynx
  • Cancer of the Hypopharynx

• • Cetuximab may also be used as a single agent as sequential systemic therapy/radiation after induction chemotherapy ‡

• • Cancer of the Lip (Mucosa)
  • Cancer of the Nasopharynx
  • Cancer of the Oral Cavity
  • Cancer of the Oropharynx

• • Cetuximab may also be used as a single agent as sequential systemic therapy/radiation after induction chemotherapy ‡

• • Cancer of the Supraglottic Larynx
  • Ethmoid Sinus Tumors
  • Maxillary Sinus Tumors
  • Very Advanced Head and Neck Cancer (i.e., newly diagnosed locally advanced T4b (M0) disease, newly diagnosed unresectable nodal disease, metastatic disease at initial presentation (M1), recurrent or persistent disease, or patients unfit for surgery)
    • Cetuximab may also be used as one of the following:

• • • First-line therapy or subsequent therapy as a single agent for non-nasopharyngeal cancer
    • Subsequent therapy in combination with platinum-based therapy (except for locoregional recurrence without prior radiation therapy)
    • Sequential systemic therapy/radiation in patients with non-nasopharyngeal cancer as a single agent following induction therapy or combination systemic therapy for recurrent disease

Occult Primary Head and Neck Cancers ‡ 

• Used as initial treatment as a single agent as sequential systemic therapy/radiation following induction chemotherapy

Squamous Cell Skin Cancer ‡ 

• Used for inoperable or incompletely resected regional disease; AND
  • Used in combination with radiation therapy (RT); OR
  • Used as a single agent if curative RT not feasible AND if patient is ineligible for immune checkpoint inhibitors and clinical trials; OR
• Used for regional recurrence or distant metastases if patient is ineligible for immune checkpoint inhibitors and clinical trials

Penile Cancer ‡ 

• Used as a single agent; AND
• Used as subsequent therapy for metastatic disease

Non-Small Cell Lung Cancer (NSCLC) ‡ 

• Patient has recurrent, advanced, or metastatic disease (excluding locoregional recurrence or symptomatic local disease without evidence of disseminated disease) or mediastinal lymph node recurrence with prior radiation therapy; AND
• Used in combination with afatinib; AND
• Used as subsequent therapy for sensitizing EGFR mutation-positive tumors; AND
• Patient has progressed on EGFR tyrosine kinase inhibitor therapy (e.g., erlotinib, afatinib, gefitinib, dacomitinib, osimertinib, etc.); AND
  • Patient has asymptomatic disease, symptomatic brain lesions, or isolated symptomatic systemic lesions; OR
  • Patient has multiple symptomatic systemic lesions; AND
    • Patient is T790M negative; OR
    • Patient is T790M positive and has progressed on second-line osimertinib therapy

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

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

IV. Renewal Criteria 

Coverage can be renewed based upon the following criteria:

• Patient continues to meet indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: anaphylactic reactions, severe infusion reactions, cardiopulmonary arrest, pulmonary toxicity/interstitial lung disease, dermatologic toxicity, hypomagnesemia/electrolyte abnormalities, etc.

V. Dosage/Administration 

VI. Billing Code/Availability Information

HCPCS Code:

• J9055 – Injection, cetuximab, 10 mg; 1 billable unit = 10 mg

NDC(s):

• Erbitux 100 mg/50 mL single-use vial; solution for injection: 66733-0948-xx
• Erbitux 200 mg/100 mL single-use vial; solution for injection: 66733-0958-xx

VII. References

1. Erbitux [package insert]. Branchburg, NJ; ImClone LLC; December 2019; Accessed October 2020.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) cetuximab. 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 October 2020.
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 4.2020. 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 October 2020.
13. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Rectal Cancer. Version 6.2020. 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 October 2020.
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 8.2020. 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 August 2020.
25. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Head and Neck Cancers. 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 October 2020.
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 October 2020.
27. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Squamous Cell Skin 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 October 2020.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: http://www.cms.gov/medicare-coverage-database/search/advanced-search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A