Last Review Date: 02/04/2025

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, 03/2021, 05/2021, 09/2021, 12/2021, 03/2022, 06/2022, 09/2022, 12/2022, 03/2023, 06/2023, 09/2023, 12/2023, 03/2024, 05/2024, 8/2024, 11/2024, 02/2025

1. Length of Authorization ^1,30

Coverage will be provided for 6 months and may be renewed, (unless otherwise specified).

Head and Neck Cancer

• In combination with radiation therapy: Coverage will be provided starting one week prior and for the duration of radiation therapy (up to 8 total weeks).
• Sequential systemic therapy/radiation: Coverage will be provided for up to 12 weeks of therapy.

2. Dosing Limits

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

• Colorectal Cancer & Head and Neck Cancer: 280 billable units every 28 days
• NSCLC: 130 billable units every 14 days
• Squamous Cell Skin Cancer & Penile Cancer
  • Loading Dose: 100 billable units for 1 dose
  • Maintenance Dose: 60 billable units every 7 days

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Colorectal Cancer (CRC) † ‡ ^{1,2,12,13,32,37}

• 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 both KRAS and NRAS mutation negative (wild-type) and BRAF V600E mutation negative (wild-type) disease as determined by an FDA-approved or CLIA-compliant testv; AND
    • Used as primary treatment for metastatic or unresectable (or medically inoperable) disease; AND
      • Used in combination with FOLFIRI †; OR
      • Used in combination with CapeOX or FOLFOX §; AND

• • • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
    • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
      • Patient is not a candidate for or has progressed on checkpoint inhibitor immunotherapy; OR

• • • • Used in combination with irinotecan; AND
  • Patient previously received FOLFOX or CapeOX within the past 12 months; AND
  • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
    • Used as primary treatment for T3, N Any; T1-2, N1-2; T4, N Any rectal cancer; AND
      • Used in combination with CapeOX, FOLFOX, or FOLFIRI; AND

• • • Used if resection is contraindicated following total neoadjuvant therapy; AND
      • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
      • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
        • Patient is not a candidate for or has progressed on checkpoint inhibitor immunotherapy; OR
    • Used if resection is contraindicated following neoadjuvant/definitive immunotherapy; AND
      • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease; OR

• • • Used for progression on non-intensive therapy, except if received previous fluoropyrimidine, with improvement in functional status §; AND

• Used in combination with FOLFOX, CapeOx, or FOLFIRI; AND

• Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
• Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND

• Patient is not a candidate for or has progressed on checkpoint inhibitor immunotherapy; OR
  • • Used as subsequent therapy for advanced or metastatic disease; AND
      • • • • •  
    • Used as a single agent; AND

• • • Patient has oxaliplatin- and irinotecan-refractory disease †; OR
    • Patient has irinotecan-intolerant disease †; OR
      • • • • • Used in combination with irinotecan; AND
    • Patient has irinotecan-refractory disease †; OR
    • Patient has oxaliplatin-refractory disease or oxaliplatin- and irinotecan-refractory disease; AND
      • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
      • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
        • Patient is not a candidate for or has progressed on checkpoint inhibitor immunotherapy; OR

• Patient has colon cancer that is refractory to therapy without irinotecan or oxaliplatin; AND

• Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
• Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND

• Patient is not a candidate for or has progressed on checkpoint inhibitor immunotherapy; OR
  • • • • • • •  
    • Used in combination with FOLFIRI for oxaliplatin-refractory disease; AND
    • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
    • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
      • Patient is not a candidate for or has progressed on checkpoint inhibitor immunotherapy; OR
        • • • •  
      • Used in combination with FOLFIRI for colon cancer that is refractory to therapy without irinotecan or oxaliplatin; AND

• Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
• Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
  • • • Patient is not a candidate for or has progressed on checkpoint inhibitor immunotherapy; OR
        • • • •  
      • Used in combination with FOLFOX or CapeOX for irinotecan-refractory disease; AND
    • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
    • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
      • Patient is not a candidate for or has progressed on checkpoint inhibitor immunotherapy; OR
  • Patient has BRAF V600E mutation positive disease as determined by an FDA-approved or CLIA-compliant testv †; AND
    • Used in combination with encorafenib; AND
    • Used as initial treatment for unresectable metastatic disease after previous FOLFOX or CapeOX within the past 12 months; AND

• • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
    • • Used as subsequent therapy for progression after at least one prior line of treatment in the advanced or metastatic disease setting; OR
    • Used in combination with encorafenib AND mFOLFOX6; AND
      • Patient has metastatic disease; OR
• Patient has KRAS G12C mutation positive disease as determined by an FDA-approved or CLIA-compliant testv ‡; AND
  • • Used in combination with sotorasib or adagrasib; AND
      • Used as initial treatment for unresectable metastatic disease after previous FOLFOX or CapeOX within the past 12 months; AND
        • • • •  
      • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR

• Used as subsequent therapy for progression of advanced or metastatic disease; AND
  • • • • • • •  
      • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
      • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
      • Patient is not a candidate for or has progressed on checkpoint inhibitor immunotherapy

§ Colon cancer patients must have left-sided tumors only.

Head and Neck Cancer † ‡ Ф ^1,2,25,29-31

• Patient has squamous cell carcinoma; AND
  • Used in combination with radiation therapy as a single agent †; OR
  • Used as sequential systemic therapy/radiation as a single agent; AND
    • Used following induction chemotherapy for one of the following cancers:
      • Cancer of the hypopharynx (T4a, N0-3 only)
      • Cancer of the oropharynx
      • Ethmoid sinus tumors** (for newly diagnosed T3, T4a disease)
      • Very advanced head and neck cancers* (non-nasopharyngeal and performance status [PS] 0-1)
      • Occult primary cancer (for p16 (HPV)-positive); AND
        • N1 (single node >3 cm, or 2 or more ipsilateral nodes ≤6 cm) disease; OR
        • N2 disease; OR
        • N3 disease; OR
    • Used following combination systemic therapy for very advanced head and neck cancers* (non-nasopharyngeal); OR
  • Used as first-line therapy; AND
    • Used in combination with platinum-based therapy for unresectable, recurrent/persistent, or metastatic disease †; OR
    • Used as a single agent for very advanced head and neck cancer* (non-nasopharyngeal); OR
    • Used in combination with paclitaxel with or without platinum-based therapy for very advanced head and neck cancers* (non-nasopharyngeal) AND PS 0-1; OR
    • Used in combination with nivolumab or pembrolizumab for very advanced head and neck cancer* (non-nasopharyngeal) AND PS 0-1; OR
  • Used as subsequent therapy; AND
    • Used as a single agent for unresectable, recurrent/persistent, or metastatic disease †; OR
    • Used in combination with carboplatin for cancer of the nasopharynx (T1-4, N0-3, M1 only), if not previously used; OR
    • Used in combination with paclitaxel with or without platinum-based therapy for very advanced head and neck cancers* (non-nasopharyngeal) AND PS 0-1; OR
    • Used in combination with platinum-based therapy, nivolumab, or pembrolizumab for very advanced head and neck cancer* (non-nasopharyngeal) AND PS 0-1; OR
    • Used in combination with carboplatin for very advanced head and neck cancer* (nasopharyngeal) AND PS 0-1

* Very Advanced Head and Neck Cancers include: newly diagnosed locally advanced T4b [M0] disease; newly diagnosed unresectable regional nodal disease, typically N3; metastatic disease at initial presentation [M1]; or recurrent or persistent disease.

** Ethmoid sinus tumors may also have adenocarcinoma, esthesioneuroblastoma, undifferentiated carcinoma (sinonasal undifferentiated carcinoma [SNUC], small cell, or sinonasal neuroendocrine carcinoma [SNEC]), or minor salivary gland histology.

Squamous Cell Skin Cancer ‡ ^2,27

• Used as a single agent in combination with radiation therapy; AND
  • Patient has locally advanced or unresectable disease; AND
    • Used as primary treatment for non-surgical candidates; OR
    • Used as additional treatment if positive surgical margins and re-resection not feasible; OR
  • Patient has resected high-risk regional disease of the head and neck with pathologic extranodal extension (ENE) or incompletely excised nodal disease; OR
  • Patient has regional disease that is unresectable, inoperable, or incompletely resected; OR
  • Patient has regional recurrence or distant metastatic disease; OR
• Used as a single agent OR in combination with carboplatin and paclitaxel; AND
  • Patient is not a candidate for or has progressed on immune checkpoint inhibitors AND clinical trials; AND
    • Patient has locally advanced or unresectable disease; AND
      • • • • •  
    • Used as primary treatment if curative surgery and curative radiation therapy (RT) are not feasible; OR
    • Used as additional treatment if positive surgical margins and curative surgery and curative RT are not feasible; OR
    • Patient has regional disease that is unresectable, inoperable, or incompletely resected if curative RT is not feasible; OR
    • Patient has regional recurrence or distant metastatic disease

Penile Cancer ‡ ^2,26

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

Non-Small Cell Lung Cancer (NSCLC) ‡ ^2,24

• Used in combination with afatinib; AND
• 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 as subsequent therapy; AND
• Patient has EGFR exon 19 deletion or exon 21 L858R or EGFR S768I, L861Q, and/or G719X mutation positive tumors as determined by an FDA-approved or CLIA-compliant testv; AND
• Patient progressed on EGFR tyrosine kinase inhibitor therapy; AND
  • Patient has asymptomatic disease, symptomatic brain lesions, or symptomatic systemic limited* progression; AND
    • Used following progression on subsequent therapy with erlotinib, afatinib, gefitinib, or dacomitinib therapy; AND
      • • • • •  
      • Patient has T790M negative disease; OR

• • • Used following subsequent therapy with continuation of osimertinib; OR

• • • Used following subsequent therapy with continuation of amivantamab-vmjw and lazertinib; AND
      • • • • •  
      • Patient has EGFR exon 19 deletion or exon 21 L858R positive disease; OR

• • Patient has multiple symptomatic systemic lesions or symptomatic systemic limited* progression; AND
    • Used following initial therapy with erlotinib, afatinib, gefitinib, or dacomitinib therapy; AND
      • • • • •  
      • Patient has T790M negative disease; OR
    • Used following initial therapy with osimertinib; OR
    • Used following initial therapy with amivantamab-vmjw and lazertinib; AND
      • • • • •  
      • Patient has EGFR exon 19 deletion or exon 21 L858R positive disease

* Limited progression: Up to 3 to 5 progressing sites.

vIf confirmed using an FDA approved assay – http://www.fda.gov/companiondiagnostics

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

4. Renewal Criteria ^1,30

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Duration of authorization has not been exceeded (refer to Section I); 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: severe infusion reactions/anaphylactic reactions, cardiopulmonary arrest, pulmonary toxicity/interstitial lung disease, dermatologic toxicity, hypomagnesemia/electrolyte abnormalities, etc.

5. Dosage/Administration ^{1,12,13,20-23,29-36}

6. Billing Code/Availability Information

HCPCS Code:

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

NDC(s):

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

7. References

1. Erbitux [package insert]. Branchburg, NJ; ImClone LLC; September 2021; Accessed January 2025.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) cetuximab. National Comprehensive Cancer Network, 2025. 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 2025.
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 4th American Society of Clinical Oncology Annual Meeting (ASCO). May 30–June 3, 2008. Chicago, Illinois.
4. Mrabti H, La Fouchardiere C, Desseigne F, et al. 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 https://www.hoparx.org/about-us/advocacy-awareness/issue-briefs/.
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 5.2024. National Comprehensive Cancer Network, 2025. 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 2025.
13. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Rectal Cancer. Version 4.2024. National Comprehensive Cancer Network, 2025. 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 2025.
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. Vermorken 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 3.2025. National Comprehensive Cancer Network, 2025. 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 2025.
25. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Head and Neck Cancers. Version 1.2025. National Comprehensive Cancer Network, 2025. 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 2025.
26. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Penile Cancer. Version 2.2025. National Comprehensive Cancer Network, 2025. 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 2025.
27. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Squamous Cell Skin Cancer. Version 1.2024. National Comprehensive Cancer Network, 2025. 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 2025.
28. Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med. 2019 Oct 24;381(17):1632-1643. doi: 10.1056/NEJMoa1908075. Epub 2019 Sep 30.
29. Chung C, Li J, Steuer C, et al. Phase II Multi-institutional Clinical Trial Result of Concurrent Cetuximab and Nivolumab in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. Clin Cancer Res. 2022 Jun 1;28(11):2329-2338. doi: 10.1158/1078-0432.CCR-21-3849.
30. Mesía R, Vázquez S, Grau JJ, et al; Spanish Head and Neck Cancer Cooperative Group (TTCC). A Phase 2 Open Label, Single-Arm Trial to Evaluate the Combination of Cetuximab Plus Taxotere, Cisplatin, and 5-Flurouracil as an Induction Regimen in Patients With Unresectable Squamous Cell Carcinoma of the Head and Neck. Int J Radiat Oncol Biol Phys. 2016 Feb 1;94(2):289-96.
31. Sacco AG, Chen R, Worden FP, et al. Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, multi-arm, non-randomised, multicentre, phase 2 trial. Lancet Oncol 2021;22:883-892.
32. Yaeger R, Weiss J, Pelster M, et al. Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C. N Engl J Med 2023;388:44- 54.
33. Carinato H, Burgy M, Ferry R, et al. Weekly Paclitaxel, Carboplatin, and Cetuximab as First-Line Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma for Patients Ineligible to Cisplatin-Based Chemotherapy: A Retrospective Monocentric Study in 60 Patients. Front Oncol. 2021 Oct 27;11:714551. doi: 10.3389/fonc.2021.714551.
34. Tahara M, Kiyota N, Yokota T, et al. Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02). Ann Oncol. 2018 Apr 1;29(4):1004-1009. doi: 10.1093/annonc/mdy040.
35. Geraghty L, Schultz TE, Hoffman SE, et al. Weekly vs. 3-weekly paclitaxel, carboplatin, and cetuximab (PCC) in recurrent/metastatic head and neck cancer. Mol Clin Oncol. 2021 Nov;15(5):240. doi: 10.3892/mco.2021.2403.
36. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Cetuximab: Head and Neck Cancers, HDN134. National Comprehensive Cancer Network, 2025. 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 Guidelines, go online to NCCN.org. Accessed January 2025.
37. Kopetz S, Yoshino T, Kim TW, et al. BREAKWATER: An open-label, multicenter, randomized, phase 3 study, with a safety lead-in (SLI), of first-line (1L) encorafenib (E) + cetuximab (C) ± chemotherapy (CT) vs standard-of-care (SOC) CT for BRAF V600E-mutant metastatic colorectal cancer (mCRC). Journal of Clinical Oncology Volume 41, Number 16_suppl. https://doi.org/10.1200/JCO.2023.41.16_suppl.TPS3627

Appendix 1 – Covered Diagnosis Codes

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

The preceding information is intended for non-Medicare coverage determinations. 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 Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

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