Notification



Notification Issue Date:



Policy Attachment

Attachment to Policy # MA08.031d


Attachment:A

Policy #:MA08.031d

Description:Dosing and Frequency Requirements

Title:Cetuximab (Erbitux®)

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.


DOSING AND FREQUENCY REQUIREMENTS

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this Policy to ensure consistency with the most recently published recommendations for the use of cetuximab (Erbitux®). Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of cetuximab (Erbitux®) outside of the Dosing and Frequency Requirements listed in this Policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for cetuximab (Erbitux®).

DOSING AND FREQUENCY REQUIREMENTS FOR CETUXIMAB (ERBITUX®)

Indication
Dosing and Frequency
Colorectal Cancer (metastatic)4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 19, 22

Metastatic Colorectal Cancer (mCRC)

Cetuximab (Erbitux®) in combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin):
  • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity. 1

Cetuximab (Erbitux®) in combination with irinotecan in individuals who previously failed or are refractory to irinotecan-based chemotherapy:
  • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity. 1

Cetuximab (Erbitux®) as a single agent in individuals who are intolerant to irinotecan or after failure of both irinotecan-based and oxaliplatin-based chemotherapy:
  • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity. 1

Colon Cancer

Cetuximab (Erbitux®) used in combination with FOLFIRI (infusional fluorouracil, leucovorin, irinotecan) or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimens for the following for left-sided only tumors that express the KRAS/NRAS/BRAF wild-type gene:
  • As primary therapy for locally unresectable or medically inoperable disease, use either regimen:
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.20, 27, 51
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 20, 27, 51
  • For unresectable synchronous liver and/or lung metastases that remain unresectable after primary systemic therapy, use either regimen:
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.20, 27, 51
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 20, 27, 51
  • As primary treatment for synchronous abdominal /peritoneal metastases that are nonobstructing, or following local therapy for individuals with imminent or existing obstruction, use either regimen:
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.20, 27, 51
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 20, 27, 51
  • For unresectable synchronous metastases of other sites, use either regimen:
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.20, 27, 51
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 20, 27, 51
  • As primary treatment for unresectable metachronous metastases in individuals who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months, who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy, or who have not received any previous chemotherapy, use either regimen:
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.20, 27, 51
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity.20, 27, 51
  • For unresectable metachronous metastases that remain unresectable after primary treatment, use either regimen:
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.20, 27, 51
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 20, 27, 51

Cetuximab (Erbitux®) used as primary treatment for unresectable synchronous liver and/or lung metastases (KRAS/NRAS/BRAF wild-type gene and left-sided tumors only) in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimen FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen
  • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.20, 27, 51
  • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 20, 27, 51

Cetuximab (Erbitux®) used in combination with irinotecan or FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) as primary treatment in individuals with unresectable metachronous metastases (KRAS/NRAS/BRAF wild-type gene and left-sided tumors only) and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months, use either regimen:
  • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.20, 27, 29, 30, 33
  • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity.20, 21, 27, 29, 30, 33

Cetuximab (Erbitux®) used as primary treatment in combination with irinotecan and vemurafenib for patients with unresectable metachronous metastases (BRAF V600E mutation positive) and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months
  • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity.20, 54

Cetuximab (Erbitux®) for the treatment of tumors that expresses the KRAS/NRAS/BRAF wild-type gene in individuals who have unresectable advanced or metastatic disease and have not previously received cetuximab or panitumumab when administered:
  • In combination with irinotecan or with FOLFIRI (infusional fluorouracil, leucovorin, irinotecan) after the first progression in individuals who previously received oxaliplatin-based regimens without irinotecan, use either regimen:
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.20, 27, 29, 30, 33
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 20, 27, 29, 30, 33
  • In combination with irinotecan or FOLFOX (fluorouracil, leucovorin, and irinotecan) regimen if previously treated with irinotecan-based therapy without oxaliplatin
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.20, 29, 30, 33
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 20, 29, 30, 33
  • In combination with irinotecan in individuals previously treated with FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen, use either regimen:
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.20, 29, 30, 33
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 20, 29, 30, 33
  • In combination with irinotecan in individuals previously treated with a fluoropyrimidine without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.20, 29, 30, 33
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 20, 29, 30, 33

Cetuximab (Erbitux®) for subsequent therapy in combination with irinotecan and vemurafenib for progression of unresectable advanced or metastatic disease (BRAF V600E mutation positive) not previously treated with cetuximab or panitumumab, in individuals previously treated with:
  • oxaliplatin-based therapy without irinotecan
  • irinotecan-based therapy without oxaliplatin
  • FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen
  • a fluoropyrimidine without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity.20, 54

Cetuximab (Erbitux®) for subsequent therapy in combination with dabrafenib and trametinib or with encorafenib and binimetinib for progression of unresectable advanced or metastatic disease (BRAF V600E mutation positive) not previously treated with cetuximab or panitumumab, in individuals previously treated with:
  • oxaliplatin-based therapy without irinotecan
  • irinotecan-based therapy without oxaliplatin
  • FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen
  • a fluoropyrimidine without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.20, 31, 55
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 20, 31, 55

Rectal Cancer

Cetuximab (Erbitux®) used in combination with FOLFIRI (infusional fluorouracil, leucovorin, irinotecan) or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimens for the following for tumors that express the KRAS/NRAS/BRAF wild-type gene:
  • As primary treatment for T3, N Any; T1-2, N1-2; T4, N Any; or locally unresectable or medically inoperable disease if resection is contraindicated following neoadjuvant therapy
  • For synchronous liver only and/or lung only metastases that are unresectable or medically inoperable and remain unresectable (with no progression of primary tumor) after primary systemic therapy
  • Following short-course radiation therapy (RT) or chemo/RT for synchronous liver only and/or lung only metastases that are unresectable or medically inoperable and remain unresectable (with progression of primary tumor) after primary systemic therapy
  • As primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for patients with existing or imminent obstruction
  • As primary treatment for synchronous unresectable metastases of other sites
  • As primary treatment for unresectable metachronous metastases in patients who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months, who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy, or who have not received any previous chemotherapy
  • For unresectable metachronous metastases that remain unresectable after primary treatment
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.38, 42, 53
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity.38, 42, 53

Cetuximab (Erbitux®) for the primary treatment of synchronous liver only and/or lung only metastases (KRAS/NRAS/BRAF wild-type gene only) that are unresectable or medically inoperable, in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimen
  • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.38, 42, 53
  • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity.38, 42, 53

Cetuximab (Erbitux®) used in combination with irinotecan or FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen in individuals with unresectable metachronous metastases and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months for tumors that express the KRAS/NRAS/BRAF wild-type gene, use either regimen:
  • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.3, 38, 39, 40, 42
  • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 3, 21, 38, 39, 40, 42
Cetuximab (Erbitux®) used in combination with irinotecan and vemurafenib for individuals with unresectable metachronous metastases (BRAF V600E mutation positive) and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months
  • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 56

Cetuximab (Erbitux®) as subsequent therapy for progression of unresectable advanced or metastatic disease (KRAS/NRAS/BRAF wild-type gene only) not previously treated with cetuximab or panitumumab
  • in combination with irinotecan or with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen if previously treated with oxaliplatin-based therapy without irinotecan
  • in combination with irinotecan or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimen if previously treated with irinotecan-based therapy without oxaliplatin
  • in combination with irinotecan if previously treated with FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen
  • in combination with irinotecan if previously treated with a fluoropyrimidine without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.3, 38, 39, 40, 42
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 3, 21, 38, 39, 40, 42

Cetuximab (Erbitux®) as subsequent therapy in combination with irinotecan and vemurafenib for progression of unresectable advanced or metastatic disease (BRAF V600E mutation positive) not previously treated with cetuximab or panitumumab, in individuals previously treated with:
  • oxaliplatin-based therapy without irinotecan
  • irinotecan-based therapy without oxaliplatin
  • FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen
  • a fluoropyrimidine without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity. 56

Cetuximab (Erbitux®) as subsequent therapy in combination with dabrafenib and trametinib or with encorafenib and binimetinib for progression of unresectable advanced or metastatic disease (BRAF V600E mutation positive) not previously treated with cetuximab or panitumumab, in individuals previously treated with:
  • oxaliplatin-based therapy without irinotecan
  • irinotecan-based therapy without oxaliplatin
  • FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen
  • a fluoropyrimidine without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab
    • Standard dosage of 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2. Continue until disease progression or unacceptable toxicity.24, 43
    • 500 mg/m2 every two weeks until disease progression or unacceptable toxicity.24, 43
Head and Neck Cancers19, 23Cetuximab (Erbitux®) used in combination with radiation therapy for the treatment of locally or regionally advanced squamous cell cancer of the head and neck:
  • 400 mg/m2 administered one week prior to initiation of a course of radiation therapy. The subsequent weekly dose (all other infusions) is 250 mg/m2. Cetuximab (Erbitux®) administration continues for the duration of radiation therapy (6 to 7 weeks)1, 25

Cetuximab (Erbitux®) used in combination with platinum-based therapy with 5-FU for the first-line treatment of recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck:
  • 400 mg/m2 administered on the day of initiation of platinum-based therapy with 5-FU. The subsequent weekly dose (all other infusions) is 250 mg/m2. Cetuximab (Erbitux®) administration continues until disease progression or unacceptable toxicity1, 25

Cetuximab (Erbitux®) administered as a single agent for the treatment of recurrent or metastatic squamous cell cancer of the head and neck in individuals who previously failed or are refractory to platinum-based chemotherapy:
  • 400 mg/m2 as an initial dose. The subsequent weekly dose (all other infusions) is 250 mg/m2 until disease progression or unacceptable toxicity1, 17, 18

Cetuximab (Erbitux®) administered as a single agent is indicated for the treatment of non-nasopharyngeal cancer with sequential chemoradiation following induction chemotherapy for the following:
  • Individuals who have newly diagnosed T4b, N0-3, M0 disease, unresectable nodal disease with no metastases, who are unfit for surgery, or unresectable locoregional recurrence and who have not received prior radiation therapy with performance status (PS) 0-1.
  • Individuals with resectable locoregional recurrence and who have not received prior radiation therapy.
    • 400 mg/m2 as an initial dose one week prior to starting radiation, followed by 250 mg/m2 weekly for 7 weeks with concurrent radiation41

Cetuximab (Erbitux®) is indicated for the systemic first-line, second-line, or subsequent treatment of non-nasopharyngeal cancer as a single agent for individuals with newly diagnosed T4b, N0-3, M0 disease, unresectable nodal disease with no metastases, unresectable locoregional recurrence and no prior radiation therapy (RT), or for individuals who are unfit for surgery and performance status (PS) 3.
  • 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2 until disease progression or unacceptable toxicity32, 35

Cetuximab (Erbitux®) is indicated as systemic first-line, second-line, or subsequent treatment as a single agent (non-nasopharyngeal cancer) in PS 0-2 individuals or in combination (PS 0-1) with carboplatin (nasopharyngeal cancer) or cisplatin (non-nasopharygeal cancer) alone, or in combination with cisplatin or carboplatin and either fluorouracil (both NCCN-preferred regimens), docetaxel, or paclitaxel (non-nasopharyngeal cancer) for metastatic (M1) disease at initial presentation, recurrent/persistent disease with distant metastases, or unresectable locoregional recurrence or second primary with prior RT.
  • As a single agent35, in combination with cisplatin36, 45, 46, with cisplatin/fluorouracil17, 37, carboplatin/fluorouracil17, 34, 47: 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2 until disease progression or unacceptable toxicity32, 44

Cetuximab administered as a single agent is indicated for the treatment of cancer of the glottic larynx with T3, N0-3 disease requiring (amenable to) total laryngectomy (consider for selected individuals with T4a who decline surgery) with primary concurrent chemoradiation:
  • 400 mg/m2 as an initial dose one week prior to starting radiation, followed by 250 mg/m2 weekly for 7 weeks with concurrent radiation28

Cetuximab administered as a single agent is indicated for the treatment of cancer of the hypopharynx:
  • With primary concurrent chemoradiation for T1, N+
  • With primary concurrent chemoradiation for T2-3, N0-3 disease requiring (amenable to) pharyngectomy with partial or total laryngectomy
  • As sequential chemoradiation for T4a, N0-3 disease with partial response at the primary site and stable or improved disease in the neck following induction chemotherapy (consider for selected individuals with T4a, N0-3 following a complete response at the primary site and stable or improved disease in the neck following induction chemotherapy)
    • 400 mg/m2 as an initial dose one week prior to starting radiation, followed by 250 mg/m2 weekly for 7 weeks with concurrent radiation28, 41

Cetuximab (Erbitux®) used in combination with carboplatin is indicated as primary therapy for the treatment of T1-4, N0-3, M1 cancer of the nasopharynx.
  • 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2 until disease progression or unacceptable toxicity47

Cetuximab (Erbitux®) administered as a single agent is indicated for the treatment of cancer of the oropharynx for the following:
  • With primary concurrent28 or sequential41 chemoradiation for either p16-negative T3-4a, N0-1 disease, or p16-negative T1-4, N2-3 disease
  • With primary concurrent28 or sequential41 chemoradiation for one of the following p16 (HPV)-positive disease:
    • T1-2, N1 (single node >3 cm, or 2 or more ipsilateral nodes ≤6 cm), T1-2, N2 or T3, N0-2 disease
    • T1-3, N3 or T4, N0-3 disease (as an NCCN-preferred regimen for primary concurrent chemoradiation)
  • 400 mg/m2 as an initial dose one week prior to starting radiation, followed by 250 mg/m2 weekly for 7 weeks with concurrent radiation28, 41

Cetuximab administered for initial definitive treatment for occult primary with sequential chemoradiation following induction chemotherapy for N2-3 disease:
  • 400 mg/m2 as an initial dose one week prior to starting radiation, followed by 250 mg/m2 weekly for 7 weeks with concurrent radiation41
Non-Melanoma Skin Cancer Cetuximab administered for the treatment of squamous cell skin cancer for inoperable positive regional lymph nodes, regional recurrence, or distant metastases:
  • 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2 until disease progression or unacceptable toxicity2, 48, 50
Non-Small Cell Lung CancerIn combination with afatinib as subsequent therapy for recurrent, advanced or metastatic disease in individuals with a known sensitizing EGFR mutation:
  • who have progressed on EGFR tyrosine kinase inhibitor therapy for asymptomatic disease, symptomatic brain lesions, or isolated symptomatic systemic lesions.
  • who are T790M negative, have progressed on EGFR tyrosine kinase inhibitor therapy, and have multiple symptomatic systemic lesions.
    • 500 mg/m2 on day 1 of a 14 day cycle until disease progression or unacceptable toxicity26, 52
Penile Cancer50 Cetuximab (Erbitux®) as single agent therapy for subsequent-line systemic treatment of metastatic disease for the treatment of penile cancer:
  • 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2 until disease progression or unacceptable toxicity49, 50

References:

1. Erbitux® (cetuximab) [prescribing information]. 04/2019. ImClone Systems Incorporated, Eli Lilly and Company. Available at: https://www.erbitux.com/hcp/?utm_id=bi_cmp-291515677_adg-1268836665642936_ad-79302335652989_kwd-79302450469161:loc-190_dev-c_ext-&utm_source=bing&utm_medium=cpc&utm_campaign=US_HCP_Erbitux_Brand_Alone%20-%20Partners%20-%202017&utm_term=erbitux&utm_content=Alone%20-%20EX . Accessed September 5, 2019.

2. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Squamous Cell Skin Cancers. Version 2.2019. updated 10/23/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. Accessed September 6, 2019.

3. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (REC 33). Rectal cancer: irinotecan every 21 days + cetuximab. [NCCN Web site]. 07/16/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//REC33 [via subscription only]. Accessed September 9, 2019.

4. Folprecht G, Gruengberger T, Bechstein WO, et al. Tumour response and secondary resectabililty of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomized phase 2 trial. Lancet Oncol. 2010;11:38-47. Epub 2009 Nov 26.

5. Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408-1417.

6. Min BS, Kim NK, Ahn JB, et al. Cetuximab in combination with 5-fluorouracil, leucovorin and irinotecan as neoadjuvant chemotherapy in patients with initially unresectable colorectal liver metastases. Onkologie. 2007;30:637-643.

7. Lee JJ, Chu E. Update on clinical data combining capecitabine with targeted agents in newly diagnosed colorectal cancer. Clin Colorectal Cancer. 2007;7 Suppl 1:S16-20.

8. Rodel C, Arnold D, Hipp M, et al. Phase I-II trial of cetuximab, capecitabine, oxaliplatin and radiotherapy as preoperative treatment in rectal cancer. Int J Radiat Oncol Biol Phys. 2008;70:1081-1086.

9. Arnold D, Hipp M, Reese T, et al. Phase I/II study of cetuximab capecitabine and oxaliplatin (CAPOX) combined with standard radiotherapy (RTX) as neoadjuvant treatment of advanced rectal cancer (RC). Journal of Clinical Oncology 2006 ASCO Annual Meeting Proceedings (Post Meeting Edition).

10. Weiss C, Arnold D, Dellas K, et al. Preoperative radiotherapy of advanced rectal cancer with capecitabine and oxaliplatin with or without cetuximab: a pooled analysis of three prospective phase I-II trials. Int J Radiation Oncology Biol Phys. 2010 Feb 2 [Epub ahead of print].

11. Sobrero AF, Maurel J, Fehrenbacher L, et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol. 2008;10:2311-2319.

12. Wierzbicki R, Jonker DJ, Moor MJ, et al. A phase II multicenter study of cetuximab monotherapy in patients with refractory, metastatic colorectal carcinoma with absent epidermal growth factor receptor immunostaining. Invest New Drugs. 2009;Oct 15.

13. Cetuximab and best supportive care compared with best supportive care alone in treating patients with metastatic epidermal growth factor receptor-positive colorectal cancer. National Cancer Institute clinical trial.

14. Mrabti H, De La Fouchardiere C, et al. Irinotecan associated with cetuximab given every 2 weeks versus cetuximab weekly in metastatic colorectal cancer. J Cancer Res Ther. 2009;5:272-276.

15. Venook A, Niedzwicki D, Hollis D, et al. Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX) +/- cetuximab for patients with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preliminary results. J Clin Oncol. 2006;24:148s

16. Folprecht G, Gruenberger T, Hartmann JT, et al. Cetuximab plus FOLFOX6 or cetuximab plus FOLFIRI as neoadjuvant treatment of nonresectable colorectal liver metastases: a randomized multicenter study (CELIM-study). Data presented at the 2009 ASCO gastrointestinal cancers symposium. San Francisco, CA. January 16, 2009.

17. Vermorken JB, Mesnia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Eng J Med.2008;359:1116.

18. Burtness B, Goldwasser MA, Flood W, et al. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology group study. J Clin Oncol.2005;23:8646.

19. Gerber DE, Choy H. Cetuximab in combination therapy: from bench to clinic. Cancer Metastasis Rev.2010;29(1):171-180.

20. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Colon Cancer. Version 2.2019. updated 05/15/2019. Available at: http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed September 6, 2019.

21. Martin-Martorell P, Rosello S, Rodriguez-Braun E, et al. Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial. Br J Cancer. 2008;99:455-458.

22. Tabernero J, Cervantes A, Rivera F, et al. Pharmacogenomic and pharmacoproteomic studies of cetuximab in metastatic colorectal cancer: biomarker analysis of a phase I dose escalation study. J Clin Oncol.2010;28(7):1181-1189.

23. Lorch JH. Induction chemotherapy in locally advanced head and neck cancer: a new standard of care? Hematol Oncol Clin North Am.2008;22:1155-1163.

24. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (REC 81). Rectal cancer: encorafenib/binimetinib + cetuximab [NCCN Web site]. 09/03/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//REC81 [via subscription only]. Accessed September 9, 2019.

25. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol.2010;11(1):21-28.

26. Pirker R, Pereira JR, Szczesna A, et al. Cetuximab plus chemotherapy in patients with advanced non-small cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet.2009;373:1525.

27. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (COL 22). Colon cancer: FOLFIRI (Fluorouracil continuous infusion/leucovorin/irinotecan) + cetuximab. [NCCN Web site]. 08/01/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//COL22 [via subscription only]. Accessed September 6, 2019.

28. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (HDN 26). Head and neck cancers: cetuximab with concurrent radiation. [NCCN Web site]. 04/06/2017. Available at:
http://www.nccn.org/TemplateManagement/Get/446/false [via subscription only]. Accessed September 9, 2019.

29. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (COL 18). Colon cancer: irinotecan every 21 days + cetuximab. [NCCN Web site]. 08/01/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//COL18 [via subscription only]. Accessed September 6, 2019.

30. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (COL 19). Colon cancer: irinotecan every 14 days + cetuximab. [NCCN Web site]. 08/01/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//COL19 [via subscription only]. Accessed September 6, 2019.

31. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (COL 73). Colon cancer: dabrafenib/trametinib + cetuximab [NCCN Web site]. 09/03/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//COL73 [via subscription only]. Accessed September 6, 2019.

32. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Head and Neck Cancers. Version 2.2019. updated 06/28/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf . Accessed September 9, 2019.

33. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (COL 20). Colon cancer: irinotecan + cetuximab. [NCCN Website]. 08/20/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//COL20 [via subscription only]. Accessed September 6, 2019.

34. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (HDN 33). Head and neck cancers: carboplatin/fluorouracil + cetuximab. [NCCN Web site]. 04/07/2017. Available at:
https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//HDN33 [via subscription only]. Accessed September 6, 2019.

35. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (HDN 37). Head and neck cancers: cetuximab. [NCCN Web site]. 04/07/2017. Available at:
https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//HDN37 [via subscription only]. Accessed September 9, 2019.

36. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (HDN 16). Head and neck cancers: cisplatin + cetuximab. [NCCN Web site]. 04/06/2017. Available at:
https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//HDN16 [via subscription only]. Accessed September 9, 2019.

37. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (HDN 32). Head and neck cancers: cisplatin/fluorouracil + cetuximab. [NCCN Web site]. 04/06/2017. Available at:
https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//HDN32 [via subscription only]. Accessed September 9, 2019.

38. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (REC 41). Rectal cancer: FOLFIRI (Fluorouracil continuous infusion/leucovorin/irinotecan) + cetuximab. [NCCN Web site]. 07/16/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//REC41 [via subscription only]. Accessed September 9, 2019.

39. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (REC 59). Rectal cancer: irinotecan + cetuximab. [NCCN Website]. 07/16/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//REC59 [via subscription only]. Accessed September 9, 2019.

40. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (REC 34). Rectal cancer: irinotecan every 14 days + cetuximab. [NCCN Web site]. 07/16/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//REC34 [via subscription only]. Accessed September 9, 2019.

41. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (HDN 49). Head and neck cancers: cetuximab with concurrent radiation. [NCCN Web site]. 04/06/2017. Available at:
http://www.nccn.org/TemplateManagement/Get/460/false [via subscription only]. Accessed September 9, 2019.

42. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Rectal Cancer. Version 2.2019. updated 05/15/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf. Accessed September 9, 2019.

43. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (REC 83). Rectal cancer: dabrafenib/trametinib + cetuximab [NCCN Web site]. 09/03/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//REC83 [via subscription only]. Accessed September 9, 2019.

44. Price KA, Cohen EE. Current treatment options for metastatic head and neck cancer. Curr Treat Options Oncol 2012;13:35-46

45. Guigay J, Fayette J, Dillies A-F, et al. Cetuximab, docetaxel, and cisplatin (TPEx) as first-line treatment in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): Final results of phase II trial GORTEC 2008-03 [abstract]. J Clin Oncol 2012;30(Suppl 15):Abstract 5505.

46. Herbst RS, Arquette M, Shin DM, et al. Phase II multicenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck. J Clin Oncol 2005;23:5578-5587.

47. Chan AT, Hsu MM, Goh BC, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol 2005;23:3568-3576.

48. 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;29(25):3419-26.

49. Carthon BC, Ng CS, Pettaway CA, Pagliaro LC. Epidermal growth factor receptor-targeted therapy in locally advanced or metastatic squamous cell carcinoma of the penis. BJU Int. 2014;113(6):871-7.

50. National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Cetuximab (Erbitux®). [NCCN Web site]. 2019. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/PrintMatrix.aspx?AID=5 [via subscription only]. Accessed September 5, 2019.

51. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (COL 44). Colon cancer: mFOLFOX6 (Fluorouracil continuous infusion/leucovorin/oxaliplatin) + cetuximab [NCCN Web site]. 08/01/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//COL44 [via subscription only]. Accessed September 6, 2019.

52. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (NSC 69). Non-Small Cell Lung Cancer: Afatinib + cetuximab [NCCN Web site]. 03/01/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//NSC69 [via subscription only]. Accessed September 5, 2019.

53. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (REC 54). Rectal cancer: mFOLFOX6 (Fluorouracil continuous infusion/Leucovorin/Oxaliplatin) + cetuximab. [NCCN Web site]. 07/16/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//REC54 [via subscription only]. Accessed September 9, 2019.

54. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (COL 66). Colon cancer: vemurafenib/irinotecan + cetuximab [NCCN Web site]. 08/01/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//COL66 [via subscription only]. Accessed September 6, 2019.

55. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (COL 69). Colon cancer: encorafenib/binimetinib + cetuximab [NCCN Web site]. 09/03/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//COL69 [via subscription only]. Accessed September 6, 2019.

56. National Comprehensive Cancer Network (NCCN). Chemotherapy Order Template (REC 72). Rectal cancer: vemurafenib/irinotecan + cetuximab [NCCN Web site]. 08/01/2019. Available at: https://www.nccn.org/professionals/OrderTemplates/CottTemplateManagement/GetTemplateById//REC72 [via subscription only]. Accessed September 9, 2019.


Version Effective Date: 12/02/2019
Version Issued Date: 12/02/2019
Version Reissued Date: N/A

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