Medicare Advantage

Medical Policy

Policy Attachment

Attachment to Policy #

MA08.031g

Attachment:

Policy #:

MA08.031g

Description:

Dosing and Frequency Requirements

Title:

Cetuximab (Erbitux®)

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,^21,^22,^{28, 29 ,30, 31, 33, 34, 35}	Metastatic Colorectal Cancer (mCRC) Cetuximab (Erbitux) in combination with FOLFIRI (5-fluorouracil [5-FU], leucovorin [LV], irinotecan) as first-line 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 toxicity¹ 500 mg/m² every two weeks until disease progression or unacceptable toxicity¹ Cetuximab (Erbitux) in combination with FOLFOX (5-FU, LV, oxaliplatin) as first-line treatment Use: 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^3,15 Cetuximab (Erbitux) in combination with irinotecan in individuals who are refractory to irinotecan-based 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 toxicity¹ 500 mg/m² every two weeks until disease progression or unacceptable toxicity¹ Cetuximab (Erbitux) as a single agent in individuals who are intolerant to irinotecan or after failure of both irinotecan-based and oxaliplatin-based 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 toxicity¹ 500 mg/m² every two weeks until disease progression or unacceptable toxicity¹ Colon Cancer Cetuximab (Erbitux) used in combination with FOLFIRI, CapeOX (capecitabine, oxaliplatin), or FOLFOX for therapy for KRAS/NRAS/BRAF wild-type gene and left-sided only tumors in individuals appropriate for intensive therapy: As primary therapy for locally unresectable or medically inoperable disease As primary treatment for synchronous abdominal /peritoneal metastases that are nonobstructing, or following local therapy for individuals with imminent or existing obstruction For unresectable synchronous metastases of other sites As initial treatment for unresectable metachronous metastases in individuals who have not received previous FOLFOX or CapeOX within the past 12 months, who have received previous 5-FU/LV or capecitabine therapy, or who have not received any previous chemotherapy For individuals who progressed on non-intensive therapy, except if received previous fluoropyrimidine, with improvement in functional status 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^20,⁴³ 500 mg/m² every two weeks until disease progression or unacceptable toxicity^20,⁴³ 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 or FOLFIRI 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^20,⁴³ 500 mg/m² every two weeks until disease progression or unacceptable toxicity^20,⁴³ Cetuximab (Erbitux) used in combination with irinotecan or FOLFIRI as INITIAL treatment in individuals with unresectable metachronous metastases (KRAS/NRAS/BRAF wild-type gene and left-sided tumors only) and previous FOLFOX or CapeOX 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, 43 500 mg/m² every two weeks until disease progression or unacceptable toxicity^20, 43 Cetuximab (Erbitux) used as initial treatment in combination with encorafenib for individuals with unresectable metachronous metastases (BRAF V600E mutation positive) and previous FOLFOX or CapeOX 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, 43 500 mg/m² every two weeks until disease progression or unacceptable toxicity^20,⁴³ Cetuximab (Erbitux) used as initial treatment in combination with sotorasib or adagrasib for individuals with unresectable metachronous metastases (KRAS G12C mutation positive) and previous FOLFOX or CapeOX within the past 12 months Use: 500 mg/m² every 2 weeks until disease progression or unacceptable toxicity^{20, 43} Cetuximab (Erbitux) for subsequent therapy for progression of advanced or metastatic disease (KRAS/NRAS/BRAF wild-type In combination with irinotecan, FOLFIRI, or as a single agent in individuals who cannot tolerate irinotecan, if previously received oxaliplatin-based regimens without irinotecan In combination with irinotecan, FOLFOX, CapeOX, or as a single agent for individuals who cannot tolerate irinotecan if previously treated with irinotecan-based therapy without oxaliplatin: In combination with irinotecan or as a single agent for individuals who cannot tolerate irinotecan in individuals previously treated with oxaliplatin and irinotecan In combination with irinotecan or as a single agent for individuals who cannot tolerate irinotecan in individuals previously treated without irinotecan or oxaliplatin followed by FOLFOX or CapeOX with or without bevacizumab 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^20,⁴³ 500 mg/m² every two weeks until disease progression or unacceptable toxicity^20,⁴³ Cetuximab (Erbitux) for subsequent therapy (including for appendiceal adenocarcinoma) in combination with encorafenib for progression of advanced or metastatic disease (BRAF V600E mutation positive) in individuals previously treated with any of the following: Oxaliplatin-based therapy without irinotecan Irinotecan-based therapy without oxaliplatin Oxaliplatin and 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, 43} 500 mg/m² every two weeks until disease progression or unacceptable toxicity^20, 43 Cetuximab (Erbitux) for subsequent therapy (including for appendiceal adenocarcinoma) in combination with encorafenib for progression of advanced or metastatic disease (BRAF V600E mutation positive) in individuals previously treated without either of the following: Irinotecan or oxaliplatin Irinotecan or oxaliplatin followed by FOLFOX or CapeOX with or without bevacizumab 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, 43} 500 mg/m² every two weeks until disease progression or unacceptable toxicity^20, 43 Cetuximab (Erbitux) for subsequent therapy in combination with sotorasib or adagrasib for progression of advanced or metastatic disease (KRAS G12C mutation positive) in individuals previously treated with any of the following: Oxaliplatin-based therapy without irinotecan Irinotecan-based therapy without oxaliplatin Oxaliplatin and irinotecan Use: 500 mg/m² every 2 weeks until disease progression or unacceptable toxicity^{20, 43} Cetuximab (Erbitux) for subsequent therapy in combination with sotorasib or adagrasib for progression of advanced or metastatic disease (KRAS G12C mutation positive) in individuals previously treated without any of the following: Irinotecan or oxaliplatin Irinotecan or oxaliplatin followed by FOLFOX or CapeOX with or without bevacizumab Use: 500 mg/m² every 2 weeks until disease progression or unacceptable toxicity^{20, 43} Rectal Cancer Cetuximab (Erbitux) used in combination with FOLFIRI, CapeOX, or FOLFOX for tumors that express the KRAS/NRAS/BRAF wild-type gene in individuals appropriate for intensive therapy, in any of the following: 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 total neoadjuvant therapy As primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals with existing or imminent obstruction As primary treatment for synchronous unresectable metastases of other sites As primary treatment for unresectable isolated pelvic/anastomotic recurrence As initial 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 5-FU/LV or capecitabine therapy, or who have not received any previous chemotherapy For individuals who progressed on non-intensive therapy, except if received previous fluoropyrimidine, with improvement in functional status 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^{42, 43} 500 mg/m² every two weeks until disease progression or unacceptable toxicity^{42, 43} Cetuximab (Erbitux) as 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 or FOLFOX 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^{42, 43} 500 mg/m² every two weeks until disease progression or unacceptable toxicity^{42, 43} Cetuximab (Erbitux), as initial treatment, used in combination with irinotecan or FOLFIRI in individuals with unresectable metachronous metastases (KRAS/NRAS/BRAF wild-type only) and previous FOLFOX or CapeOX 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^42,⁴³ 500 mg/m² every two weeks until disease progression or unacceptable toxicity^{42, 43} Cetuximab (Erbitux) used as initial treatment in combination with sotorasib or adagrasib for individuals with unresectable metachronous metastases (KRAS G12C mutation positive) and previous FOLFOX or CapeOX within the past 12 months Use: 500 mg/m² every 2 weeks until disease progression or unacceptable toxicity^{42, 43} Cetuximab (Erbitux), as initial treatment, used in combination with encorafenib for individuals with unresectable metachronous metastases (BRAF V600E mutation positive) and previous adjuvant FOLFOX or CapeOX 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^{42, 43} 500 mg/m² every two weeks until disease progression or unacceptable toxicity^{42, 43} Cetuximab (Erbitux) as subsequent therapy for progression of advanced or metastatic disease (KRAS/NRAS/BRAF wild-type gene only): In combination with irinotecan, FOLFIRI, or as a single agent for individuals who cannot tolerate irinotecan, if previously treated with oxaliplatin-based therapy without irinotecan In combination with irinotecan, FOLFOX, CapeOX, or as a single agent for individuals who cannot tolerate irinotecan, if previously treated with irinotecan-based therapy without oxaliplatin In combination with irinotecan, or as a single agent for individuals who cannot tolerate irinotecan, if previously treated with oxaliplatin and irinotecan In combination with irinotecan, or as a single agent for individuals who cannot tolerate irinotecan, if previously treated without irinotecan or oxaliplatin followed by FOLFOX or CapeOX with or without bevacizumab 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^42,⁴³ 500 mg/m² every two weeks until disease progression or unacceptable toxicity^42,⁴³ Cetuximab (Erbitux) for subsequent therapy in combination with encorafenib for progression of advanced or metastatic disease (BRAF V600E mutation positive) in individuals previously treated with any of the following: Oxaliplatin-based therapy without irinotecan Irinotecan-based therapy without oxaliplatin Oxaliplatin and 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 toxicity⁴^{2, 43} 500 mg/m² every two weeks until disease progression or unacceptable toxicity⁴²^, 43 Cetuximab (Erbitux) for subsequent therapy in combination with encorafenib for progression of advanced or metastatic disease (BRAF V600E mutation positive) in individuals previously treated without either of the following: Irinotecan or oxaliplatin Irinotecan or oxaliplatin followed by FOLFOX or CapeOX with or without bevacizumab 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 toxicity⁴^{2, 43} 500 mg/m² every two weeks until disease progression or unacceptable toxicity⁴^2, 43 Cetuximab (Erbitux) for subsequent therapy in combination with sotorasib or adagrasib for progression of advanced or metastatic disease (KRAS G12C mutation positive) in individuals previously treated with any of the following: Oxaliplatin-based therapy without irinotecan Irinotecan-based therapy without oxaliplatin Oxaliplatin and irinotecan Use: 500 mg/m² every 2 weeks until disease progression or unacceptable toxicity⁴^{2, 43} Cetuximab (Erbitux) for subsequent therapy in combination with sotorasib or adagrasib for progression of advanced or metastatic disease (KRAS G12C mutation positive) in individuals previously treated without any of the following: Irinotecan or oxaliplatin Irinotecan or oxaliplatin followed by FOLFOX or CapeOX with or without bevacizumab Use: 500 mg/m² every 2 weeks until disease progression or unacceptable toxicity^{42, 43}
Head and Neck Cancers^{19, 23}^{, 36, 37, 38, 39, 40, 44, 45, 46, 47, 67, 68, 69, 70}	Cetuximab (Erbitux) used in combination with radiation therapy (RT) for the initial treatment of locally or regionally advanced squamous cell cancer of the head and neck Use: 400 mg/m²administered 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: Use either regimen: 400 mg/m²administered 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 toxicity^{1, 25} 500 mg/m² every two weeks until disease progression or unacceptable toxicity¹ 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 Use: 400 mg/m² as an initial dose. The subsequent weekly dose (all other infusions) is 250 mg/m² until disease progression or unacceptable toxicity^{1, 17, 18} Non-nasopharyngeal Cancer Cetuximab (Erbitux) is indicated for the treatment of non-nasopharyngeal cancer: Administered as a single agent given weekly as sequential systemic therapy/RT following induction systemic therapy for individuals with performance status (PS) 0-1 and who have one of the following: Newly diagnosed T4b, N0-3, M0 disease Newly diagnosed unresectable nodal disease with no metastases Newly diagnosed non-metastatic disease and who are unfit for surgery Unresectable locoregional recurrence or persistent disease and who have not received prior RT Use: 400 mg/m²administered 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 (7 weeks)^{32, 43} Administered as a single agent given weekly as sequential systemic therapy/RT following combination systemic therapy in individuals with resectable locoregional recurrence or persistent disease and who have not received prior RT Use 400 mg/m²administered 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 (7 weeks)^{32, 43} Administered as a single agent for the systemic first-line treatment for individuals with: PS 3 and newly diagnosed T4b, N0-3, M0 disease, newly diagnosed unresectable nodal disease with no metastases or newly diagnosed non-metastatic disease for individuals who are unfit for surgery PS 0-3 and metastatic (M1) disease at initial presentation PS 3 and unresectable locoregional recurrence or unresectable persistent disease without prior RT PS 0-3 and unresectable locoregional recurrence with prior RT, unresectable second primary with prior RT, or unresectable persistent disease with prior RT, or recurrent/persistent disease with distant metastases Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² until disease progression or unacceptable toxicity^32,⁴³ Subsequent-line treatment as a single agent for individuals with: Alternate option for PS 0-3 for metastatic (M1) disease at initial presentation PS 3 and unresectable locoregional recurrence or unresectable persistent disease without prior RT Alternate option for PS 0-3 and unresectable locoregional recurrence with prior RT, unresectable second primary with prior RT, or unresectable persistent disease with prior RT, or recurrent/persistent disease with distant metastases Use: 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2 until disease progression or unacceptable toxicity^32,⁴³ Administered as a single agent as postoperative systemic therapy/RT if cisplatin ineligible for positive margin and/or extranodal extension in: Resectable locoregional recurrence or persistent disease without prior RT Resectable locoregional recurrence, second primary, or persistent disease with prior RT Use: 400 mg/m²administered 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 (7 weeks)^{32, 43} As combination systemic first-line, or subsequent-line treatment, in individuals with PS 0-1, given: As part of any of the following regimens: 5-FU and cisplatin 5-FU and carboplatin Docetaxel and cisplatin Docetaxel and carboplatin Paclitaxel and cisplatin Paclitaxel and carboplatin Cisplatin Nivolumab Pembrolizumab Paclitaxel For any of the following: Metastatic (M1) disease at initial presentation Recurrent/persistent disease with distant metastases Unresectable locoregional recurrence with prior RT Unresectable second primary with prior RT Unresectable persistent disease with prior RT For 5-FU and cisplatin, 5-FU and carboplatin, cisplatin, pembrolizumab, or paclitaxel Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² until disease progression or unacceptable toxicity^{32, 43} For docetaxel and cisplatin or docetaxel and carboplatin Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² for a maximum of 3 cycles followed by 500 mg/m²every two weeks until disease progression or unacceptable toxicity^{32, 43} For paclitaxel and cisplatin or paclitaxel and carboplatin Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² for a maximum of 5 cycles followed by 500 mg/m²every two weeks until disease progression or unacceptable toxicity^{32, 43} For nivolumab Use: 500 mg/m² administered every 2 weeks (starting 2 weeks prior to initiation of nivolumab) until disease progression or unacceptable toxicity^{32, 43} As combination systemic therapy for resectable locoregional recurrence or persistent disease without prior RT given as part of any of the following regimens: 5-FU and cisplatin 5-FU and carboplatin Docetaxel and cisplatin Docetaxel and carboplatin Paclitaxel and cisplatin Paclitaxel and carboplatin Cisplatin Nivolumab Pembrolizumab Paclitaxel For 5-FU and cisplatin, 5-FU and carboplatin, cisplatin, pembrolizumab, or paclitaxel Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² until disease progression or unacceptable toxicity^{32, 43} For docetaxel and cisplatin or docetaxel and carboplatin Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² for a maximum of 3 cycles followed by 500 mg/m²every two weeks until disease progression or unacceptable toxicity^{32, 43} For paclitaxel and cisplatin or paclitaxel and carboplatin Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² for a maximum of 5 cycles followed by 500 mg/m²every two weeks until disease progression or unacceptable toxicity^{32, 43} For nivolumab Use: 500 mg/m² administered every 2 weeks (starting 2 weeks prior to initiation of nivolumab) until disease progression or unacceptable toxicity^{32, 43} Ethmoid Sinus Cancer Cetuximab (Erbitux) administered as a single agent given weekly is indicated for the treatment of cancer of the ethmoid sinus as sequential systemic therapy/RT following a complete response to induction chemotherapy for newly diagnosed T3, T4a disease Use: 400 mg/m²administered 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 (7 weeks)^{32, 43} Nasopharynx Cancer Cetuximab (Erbitux) used in combination with carboplatin is indicated for the treatment of very advanced cancer of the nasopharynx as systemic first-line or subsequent-line (if not previously used) treatment in individuals with PS 0-1 for: Recurrent/persistent disease with distant metastases Unresectable locoregional recurrence with prior RT Unresectable second primary with prior RT Unresectable persistent disease with prior RT Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² until disease progression or unacceptable toxicity^32,⁴³ Cetuximab (Erbitux) used in combination with carboplatin is indicated as first-line systemic therapy for the treatment of T1-4, N0-3, M1 disease for: Oligometastatic disease and PS 0-2 Widely metastatic disease and good PS (0-2) Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² until disease progression or unacceptable toxicity^32,⁴³ Cetuximab (Erbitux) used in combination with carboplatin, if not previously used, as subsequent-line systemic therapy for the treatment of T1-4, N0-3, M1 disease for: Oligometastatic disease and PS 0-2 Widely metastatic disease and good PS (0-2) Use: 400 mg/m2 as an initial dose. The subsequent weekly dose is 250 mg/m2 until disease progression or unacceptable toxicity^32,⁴³ Oral Cavity Cancer (including Mucosal Lip) Cetuximab (Erbitux) administered as a single agent is indicated for the treatment of cancer of the oral cavity (including mucosal lip) as postoperative systemic therapy/RT in individuals who are cisplatin ineligible with one of the following: Extranodal extension with or without positive margin for T1-3, N0-3; or T4a, N0-3 disease With positive margins for T3, N0; T1-3, N1-3; or T4a, N0-3 disease May be considered with positive margin in T1-2, N0 disease Use: 400 mg/m²administered 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 weeks)^{32, 43} Oropharynx Cancer Cetuximab (Erbitux) administered as a single agent is indicated for the treatment of cancer of the oropharynx for the following: As primary concurrent systemic therapy/RT for either p16-negative disease: T3-4a, N0-1 disease T1-4a, N2-3 disease As primary concurrent systemic therapy/RT for either p16 (human papillomavirus [HPV]-positive disease: T0-2, N1 (single node >3 cm, or 2 or more ipsilateral nodes 6 cm or less), T0-2, N2 or T3, N0-2 disease (treatment modality preferred if clinical evidence of fixed or matted nodes or obvious extranodal extension) T0-3, N3 or T4, N0-3 disease As sequential systemic therapy/RT given weekly following induction chemotherapy for either p16-negative T3-4a, N0-1 disease T1-4a, N2-3 disease As sequential systemic therapy/RT given weekly following induction chemotherapy for either p16 (human papillomavirus [HPV])-positive disease: T0-2, N1 (single node >3 cm, or two or more ipsilateral nodes 6 cm or less), T0-2, N2 or T3, N0-2 disease T0-3, N3 or T4, N0-3 disease Use: 400 mg/m²administered 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 (7 weeks)^{32, 43} Supraglottic Larynx Cancer Cetuximab (Erbitux) administered as a single agent is indicated for the treatment of cancer of the supraglottic larynx: Following a partial response at the primary site to induction chemotherapy given weekly for: T3, N0 and most T3, N1-3 disease requiring (amenable to) total laryngectomy T1-2, N+ and selected T3, N1 disease amenable to larynx-preserving (conservation) surgery T4a, N0-3 disease for individuals who decline surgery Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² until disease progression or unacceptable toxicity^{32, 43} As postoperative systemic therapy/RT if cisplatin ineligible for most individuals with T1-2, N0 and selected T3 disease amenable to larynx-preserving (conservation) surgery for: Extranodal extension May be considered for discovery of positive node for disease with a positive margin Use: 400 mg/m²administered 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 weeks)^{32, 43} As postoperative systemic therapy/RT if cisplatin ineligible for individuals with extranodal extension and/or positive margin for: T3, N0 and most T3, N1-3 disease requiring (amenable to) total laryngectomy T1-2, N+ and selected T3, N1 disease amenable to larynx-preserving (conservation) surgery T4a, N0-3 disease T1-2, N+ and T3-4a, N0-3 disease following surgery with less than partial response at the primary site to induction chemotherapy Use: 400 mg/m²administered 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 weeks)^{32, 43} Glottic Larynx Cancer Cetuximab (Erbitux) administered as a single agent is indicated for the treatment of cancer of the glottic larynx Following partial response at the primary site to induction chemotherapy given weekly for: T3, N0-3 disease requiring (amenable to) total laryngectomy Selected individuals with T4a who decline surgery Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² until disease progression or unacceptable toxicity^{32, 43} As postoperative systemic therapy/RT in individuals ineligible for cisplatin with extranodal extension: For T1-2, N0 or select T3, N0 disease amenable to larynx-preserving (conservation) surgery And/or positive margin for T3, N0-3 disease requiring (amenable to) total laryngectomy And/or positive margin for T3, N0-3 disease following laryngectomy and less than partial response at the primary site to induction chemotherapy And/or positive margin for T4a, N0-3 disease Use: 400 mg/m²administered 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 weeks)^{32, 43} Hypopharynx Cancer Cetuximab (Erbitux) administered as a single agent is indicated for the treatment of cancer of the hypopharynx: As primary concurrent systemic therapy/RT or induction chemotherapy for either of the following: T1, N+ disease T2-3, N0-3 disease requiring (amenable to) pharyngectomy with partial or total layngectomy Use: 400 mg/m² administered 1 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 (7 weeks)^{32, 43} As sequential systemic therapy/RT given weekly for T4a, N0-3 disease for either of the following: A partial response at the primary site and stable or improved disease in the neck following induction chemotherapy A complete response at the primary site and stable or improved disease in the neck following induction chemotherapy Use: 400 mg/m²administered 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 (7 weeks)^{32, 43} As postoperative systemic therapy/RT in individuals who are cisplatin ineligible with one of the following: Extranodal extension with or without positive margin for most T1, N0 or selected T2, N0 tumors amenable to larynx-preserving (conservation) surgery May be considered with positive margin for T2, N0 tumors amenable to larynx-preserving (conservation) surgery Use: 400 mg/m²administered 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 weeks)^{32, 43} As postoperative systemic therapy/RT in individuals who are cisplatin ineligible with extranodal extension and/or positive margin and one of the following: T1, N+ or T2-3, N0-3 disease requiring (amenable to) pharyngectomy with partial or total laryngectomy T1, N+ or T2-3, N0-3 disease with partial response and stable or improved disease in the neck or less than partial response at the primary site following induction chemotherapy T4a, N0-3 disease T4a, N0-3 disease with less than partial response at the primary site following induction chemotherapy Use: 400 mg/m²administered 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 weeks)^{32, 43} Occult Primary Head and Neck Cancer Cetuximab (Erbitux) administered as a single agent for occult primary head and neck cancer For initial definitive treatment as sequential systemic therapy/RT given weekly following induction chemotherapy for N2-3 disease with any of the following histology: Poorly differentiated or nonkeratinizing squamous cell Anaplastic (not thyroid) Squamous cell carcinoma Not otherwise specified (NOS) Use: 400 mg/m²administered 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 (7 weeks)^{32, 43} As primary concurrent systemic therapy/RT for p16 (HPV)-positive disease in any of the following: N1 (single node >3 cm, or 2 or more ipsilateral nodes 6 cm or less) disease N2 disease N3 disease Use: 400 mg/m² administered as the initial dose. The subsequent weekly dose (all other infusions) is 250 mg/m². Cetuximab (Erbitux) administration continues for the duration of radiation therapy (7 weeks)^32,43 As postoperative systemic therapy/RT if cisplatin ineligible for disease with extranodal extension after neck dissection of disease in levels IV or V with adenocarcinoma histology of neck node, thyroglobulin and calcitonin negative Use: 400 mg/m²administered 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 weeks)^{32, 43} As sequential systemic therapy/RT given weekly following induction chemotherapy for p16 (HPV)-positive disease in either of the following: N1 (single node >3 cm, or 2 or more ipsilateral nodes 6 cm or less) disease N2-3 disease Use: 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 weeks)^{32, 43}
Non-Small Cell Lung Cancer^{26, 41}	Cetuximab (Erbitux) in combination with afatinib as subsequent therapy for recurrent (excluding locoregional recurrence or symptomatic local disease with no evidence of disseminated disease; however, including mediastinal lymph node recurrence with prior RT), advanced or metastatic disease in individuals with EGFR exon 19 deletion or exon 21 L858R or EGFR S768I, L861Q, and/or G719X mutation positive disease: Who have progressed on EGFR tyrosine kinase inhibitor therapy for asymptomatic disease, symptomatic brain lesions, or symptomatic systemic limited progression Who are T790M negative, have progressed on EGFR tyrosine kinase inhibitor therapy, and have multiple symptomatic systemic lesions Who are T790M positive, who have progressed on osimertinib, and have multiple symptomatic systemic lesions Use: 500 mg/m² on day 1 of a 14 day cycle until disease progression or unacceptable toxicity^24,⁴³
Penile Cancer⁴⁹	Cetuximab (Erbitux) as single agent therapy for subsequent-line systemic treatment of metastatic/recurrent disease, especially if not treated with a similar class of agent Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² until disease progression or unacceptable toxicity^{27, 43}
Squamous Cell Skin Cancer^{48, 71, 72}	Cetuximab (Erbitux) administered for the treatment of squamous cell skin cancer: As a single agent with concurrent RT for any of the following: For locally advanced or unresectable disease as either of the following: Primary treatment for non-surgical candidates Additional treatment if positive surgical margins and re-resection not feasible Resected high-risk regional disease of the head and neck (pathologic extranodal extension [ENE] or incompletely excised nodal disease) Regional disease that is unresectable, inoperable, or incompletely resected Regional recurrence or distant metastatic disease As a single agent or in combination with carboplatin and paclitaxel if ineligible for, or progressed on, immune checkpoint inhibitors and clinical trials as treatment in any of the following: For locally advanced or unresectable disease as either of the following: Primary treatment if curative surgery and curative RT are not feasible Additional treatment if positive surgical margins and curative surgery and curative RT are not feasible Regional disease that is unresectable, inoperable, or incompletely resected if curative RT no feasible Regional recurrence or distant metastatic disease Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² until disease progression or unacceptable toxicity^{2, 43}
Additional Indications^{11, 12, 26, 46, 47, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66}	Cetuximab (Erbitux) as treatment of gastric and gastro-esophageal junction cancer when one of the following indications are met: In combination with CapeOX is indicated in individuals with untreated metastatic or locally advanced disease In combination with FOLFIRI or FOLFOX in individuals with metastatic disease Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² until disease progression or unacceptable toxicity⁵⁰ Cetuximab (Erbitux) in combination with FOLFOX or FOLFIRI used as first-line therapy for EGFR-expressing nonresectable advanced or metastatic CRC (no central nervous system metastases) Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² until disease progression or unacceptable toxicity⁵⁰ For liver metastases, can also use: 500 mg/m² on day 1 of a 14-day cycle until disease progression or unacceptable toxicity⁵⁰ Cetuximab (Erbitux) in combination with irinotecan for the treatment of mCRC, EGFR-expressing disease in individuals who failed both fluoropyrimidine- and oxaliplatin-based regimens Use: 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m² until disease progression or unacceptable toxicity⁵⁰ Cetuximab (Erbitux), either alone or in combination with irinotecan for the treatment of refractory mCRC, non-EGFR expressing 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 toxicity⁵⁰ 500 mg/m² every two weeks until disease progression or unacceptable toxicity⁵⁰ Cetuximab (Erbitux) as treatment of advanced or metastatic non-small cell lung cancer: As first-line treatment: In combination with a taxane and carboplatin In combination with cisplatin and vinorelbine for disease that is EGFR detectable for individuals without brain metastases or who have not previously been treated with either anti-EGFR therapy or a monoclonal antibody In combination with gemcitabine and a platinum-containing agent for individuals who do not have brain metastases that are symptomatic, uncontrolled, or treated with a glucocorticoid As subsequent-line treatment as monotherapy for individuals previously treated with a platinum-containing regimen who have not previously been treated with either anti-EGFR therapy or a monoclonal antibody Use: Standard dosage of 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m². Continue until disease progression or unacceptable toxicity⁵⁰ Cetuximab (Erbitux) in combination with platinum-based therapy for the treatment of metastatic or recurrent squamous cell carcinoma of the head and neck in disease that is refractory to platinum-based therapy Use: Standard dosage of 400 mg/m² as an initial dose. The subsequent weekly dose is 250 mg/m². Continue until disease progression or unacceptable toxicity⁵⁰

References:

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2. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Squamous Cell Skin Cancer. V1.2024. [NCCN website]. 11/09/2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. Accessed December 26, 2023.

3. American Hospital Formulary Service (AHFS). Drug Information 2023. Cetuximab (Erbitux®). [Lexicomp Online Web site]. 12/12/2023. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed December 26, 2023.

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 randomised phase 2 trial. Lancet Oncol. 2010;11:38-47.

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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-S20.

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;24(18):S3574.

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;78(2):472-478.

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;26(14):2311-2319.

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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, Niedzwiecki 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) [abstract]. Gastrointestinal Cancer Symposium 2009:296(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(11):1116-1127.

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

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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). NCCN Clinical Practice Guidelines in Oncology - Non-small cell lung cancer. V1.2024. [NCCN Web site]. 12/21/2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed December 26, 2023.

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(9674):1525-1531.

27. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Penile Cancer. V1.2024. [NCCN website]. 10/25/2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/penile.pdf. Accessed December 26, 2023.

28. Venook AP, Niedzwiecki D, Lenz HJ, et al. Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: a randomized clinical trial. JAMA. 2017;317(23):2392-2401.

29. 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;351(4):337-345.

30. Van Cutsem E, Tejpar S, Vanbeckevoort D, et al. Intrapatient cetuximab dose escalation in metastatic colorectal cancer according to the grade of early skin reactions: the randomized EVEREST study. J Clin Oncol. 2012;30(23):2861-2868.

31. Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N Engl J Med. 2019;381(17):1632-1643.

32. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Head and Neck Cancers. V2.2024. [NCCN website]. 12/08/2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf . Accessed December 26, 2023.

33. Kopetz S, Grothey A, Van Cutsem E, et al. Encorafenib plus cetuximab with or without binimetinib for BRAF V600E-mutant metastatic colorectal cancer: quality-of-life results from a randomized, three-arm, phase III study versus the choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC). J of Clin Onc. 2020;38(4):S8.

34. Bokemeyer C, Van Cutsem E, Rougier P, et al. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012;48(10):1466-1475.

35. Tabernero J, Ciardiello F, Rivera F, et al. Cetuximab administered once every second week to patients with metastatic colorectal cancer: a two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study. Ann Oncol. 2010;21(7):1537-1545.

36. Harari PM, Harris J, Kies MS, et al. Postoperative chemoradiotherapy and cetuximab for high-risk squamous cell carcinoma of the head and neck: Radiation Therapy Oncology Group RTOG-0234. J Clin Oncol. 2014;32(23):2486-2495.

37. Nishimura G, Hatakeyama H, Shiono O, et al. Postoperative bio-chemoradiotherapy using cetuximab and docetaxel in patients with cis-platinum-intolerant core high-risk head and neck cancer: protocol of a phase 2 nonrandomized clinical trial. JMIR Res Protoc. 2018;7(8):e11003.

38. 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;25(16):2171-2177.

39. Guigay J, Fayette J, Dillies AF, et al. Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. Ann Oncol. 2015;26(9):1941-1947.

40. Bossi P, Miceli R, Locati LD, et al. A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Ann Oncol. 2017;28(11):2820-2826.

41. Janjigian YY, Smit EF, Groen HJM, 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;4(9):1036-1045.

42. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Rectal Cancer. V6.2023. [NCCN website]. 11/16/2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf. Accessed December 26, 2023.

43. National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Cetuximab (Erbitux®). [NCCN Web site]. 2023. Available at: https://www.nccn.org/compendia-templates/compendia/drugs-and-biologics-compendia [via subscription only]. Accessed December 26, 2023.

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 AF, 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(24):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):3419-3426.

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):871-877.

50. Merative Micromedex^® DRUGDEX^® (electronic version). Cetuximab (Erbitux^®). [Micromedex Web site]. Merative L.P., Ann Arbor, Michigan, USA. 09/27/2023. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed December 26, 2023.

51. Kim C, Lee JL, Ryu MH, et al. A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer. Invest New Drugs. 2011;29(2):366-373.

52. Moehler M, Mueller A, Trarbach T, et al. Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer: a prospective multi-center biomarker-oriented phase II study. Ann Oncol. 2011;22(6):1358-1366.

53. Lordick F, Luber B, Lorenzen S, et al. Cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric cancer: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Br J Cancer. 2010;102(3):500-505.

54. Tveit KM, Guren T, Glimelius B, et al. Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol. 2012;30(15):1755-1762.

55. Bokemeyer C, Bondarenko I, Makhson A, et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009;27(5):663-671.

56. Ocvirk J, Brodowicz T, Wrba F, et al. Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial. World J Gastroenterol. 2010;16(25):3133-3143.

57. Ye LC, Liu TS, Ren L, et al. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol. 2013;31(16):1931-1938.

58. Kang MJ, Hong YS, Kim KP, et al. Biweekly cetuximab plus irinotecan as second-line chemotherapy for patients with irinotecan-refractory and KRAS wild-type metastatic colorectal cancer according to epidermal growth factor receptor expression status. Invest New Drugs. 2012;30(4):1607-1613.

59. Chung KY, Shia J, Kemeny NE, et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol. 2005;23(9):1803-1810.

60. Hebbar M, Wacrenier A, Desauw C, et al. Lack of usefulness of epidermal growth factor receptor expression determination for cetuximab therapy in patients with colorectal cancer. Anticancer Drugs. 2006;17(7):855-857.

61. Lenz HJ, Mayer RJ, Gold PJ, et al. Activity of cetuximab in patients with colorectal cancer refractory to both irinotecan and oxaliplatin. J Clin Oncol. 2004;22(14S):3510.

62. Hanna N, Lilenbaum R, Ansari R, et al. Phase II trial of cetuximab in patients with previously treated non-small-cell lung cancer. J Clin Oncol. 2006;24(33):5253-5258.

63. Lynch TJ, Patel T, Dreisbach L, et al. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol. 2010;28(6):911-917.

64. Butts CA, Bodkin D, Middleman EL, et al. Randomized phase II study of gemcitabine plus cisplatin or carboplatin, with or without cetuximab, as first-line therapy for patients with advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2007;25(36):5777-5784.

65. Rosell R, Robinet G, Szczesna A, et al. Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer. Ann Oncol. 2008;19(2):362-369.

66. Baselga J, Trigo JM, Bourhis J, et al. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2005;23(24):5568-5577.

67. Chung CH, Li J, Steuer CE, 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;28(11):2329-2338.

68. 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(6):883-892.

69. Bossi P, Micelli R, Locati LD, et al. A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Ann Oncol. 2017;28(11):2820-2826.

70. Lefebvre JL, Pointreau Y, Rolland F, et al. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol. 2013;31(7):853-859.

71. 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):3419-3426.

72. 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.

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