Cetuximab (Erbitux)

General information

Class/mechanism: EGFR antagonist; monoclonal antibody that binds to the EGFR/HER1/c-ErbB-1 receptor tyrosine kinase, competitively inhibiting binding of epidermal growth factor (EGF) and other ligands, such as transforming growth factor-alpha. This results in inhibition of cell growth, induction of apoptosis, decreased matrix metalloproteinase, and decreased vascular endothelial growth factor production.
Route: IV
Extravasation: neutral

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Resistance mechanisms

• Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008 Oct 23;359(17):1757-65. link to original article PubMed

Diseases for which it is established (work in progress)

• Colorectal cancer, BRAF-mutated
• Colorectal cancer, RAS wild-type
• Head and neck cancer

Diseases for which it is used

• Colorectal cancer
  • Rectal cancer
• Cutaneous squamous cell carcinoma
• Esophageal cancer
  • Esophageal adenocarcinoma
  • Esophageal squamous cell carcinoma
• Non-small cell lung cancer
• Pancreatic cancer

Patient drug information

• Cetuximab (Erbitux) package insert
• Cetuximab (Erbitux) patient drug information (Chemocare)
• Cetuximab (Erbitux) patient drug information (UpToDate)

History of changes in FDA dosing recommendations

• 2021-04-06: Approved a new dosage regimen of 500 mg/m² as a 120-minute intravenous infusion every two weeks (Q2W) for patients with K-Ras wild-type, EGFR-expressing colorectal cancer (mCRC).
• 2021-04-06: Approved a new dosage regimen of 500 mg/m² as a 120-minute intravenous infusion every two weeks (Q2W) for patients with squamous cell carcinoma of the head and neck (SCCHN)

History of changes in FDA indication

Colorectal cancer

• 2004-02-12: Initial accelerated FDA approval in combination with irinotecan for the treatment of EGFR-expressing, metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy. (Based on Saltz et al. 2004)
• 2004-02-12: Initial accelerated FDA approval as a single agent for the treatment of EGFR-expressing, metastatic colorectal carcinoma in patients who are intolerant to irinotecan-based chemotherapy. (Based on BOND)
• 2007-10-02: Granted regular approval for the treatment of patients with EGFR-expressing metastatic colorectal cancer (mCRC) after failure of both irinotecan- and oxaliplatin-based chemotherapy regimens. (Approval changed from accelerated to regular; based on NCIC-CTG CO.17)
• 2011-11-07: Retrospective subset analyses of metastatic or advanced colorectal cancer trials have not shown a treatment benefit for Erbitux in patients whose tumors had KRAS mutations in codon 12 or 13. Use of Erbitux is not recommended for the treatment of colorectal cancer with these mutations. (New recommendation dependent on KRAS mutant status)
• 2012-07-06: FDA indication changed for the treatment of K-Ras mutation-negative (wild-type), EGFR-expressing, metastatic colorectal cancer as determined by FDA-approved test, in combination with FOLFIRI for first-line treatment." (New requirement dependent on KRAS mutant status; based on CRYSTAL)
  • Limitation of Use: Erbitux is not indicated for treatment of K-Ras mutation-positive colorectal cancer.
• 2021-09-24: Approved in combination with encorafenib for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation. (Based on BEACON CRC)

Head and neck cancer

• 2006-03-01: Indication expanded in combination with radiation therapy, is indicated for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck. (New disease entity; based on IMCL-9815)
• 2006-03-01: Indication expanded as a single agent for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck for whom prior platinum-based therapy has failed. (Based on EMR 62202-016)
• 2011-11-07: Indication changed for the treatment of recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU. (Based on EXTREME)

History of changes in EMA indication

• 2004-06-29: Initial authorization

History of changes in Health Canada indication

• 2005-09-09: Initial notice of compliance in combination with a chemotherapy medicine, irinotecan, is indicated for the treatment of EGFR-expressing metastatic colorectal carcinoma (CRC) in patients who are refractory to other irinotecan-based chemotherapy regimens.
• 2005-09-09: Initial notice of compliance administered as a single agent, is indicated for the treatment of EGFR-expressing metastatic colorectal carcinoma in patients who are intolerant to irinotecan-based chemotherapy.
• 2008-09-11: New indication in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma of the head and neck.
• 2010-02-03: New indication (unknown details)
• 2012-12-20: New indication for the treatment of EGFR-expressing K-ras wild-type metastatic colorectal carcinoma (mCRC) in combination with FOLFIRI (irinoteca, 5-fluorouracil, leucovorin) for first-line treatment.

History of changes in PMDA indication

• 2008-07-16: Initial approval for the treatment of EGFR-expressing, unresectable and advanced/recurrent colorectal carcinomas.
• 2012-12-21: New additional indication for the treatment of head and neck cancer.
• 2019-09-20: New indication for the treatment of unresectable, advanced or recurrent colon or rectal cancer with wild-type RAS.

Also known as

• Code name: C-225
• Brand names: Cetuxim, Erbitux