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 used

• Colon cancer
• Cutaneous squamous cell carcinoma
• Esophageal cancer
• Head and neck cancer
• Non-small cell lung cancer
• Pancreatic cancer

Patient drug information

• Cetuximab (Erbitux) patient drug information (Chemocare)
• Brief patient counseling information can be found on page 8 of the package insert
• Cetuximab (Erbitux) patient drug information (UpToDate)

History of changes in FDA indication

Colorectal cancer

• 2/12/2004: Initial accelerated FDA approval:
  • in combination with irinotecan, is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy.
  • as a single agent is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma in patients who are intolerant to irinotecan-based chemotherapy.
• 10/2/2007: 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)
• 11/7/2011: 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 based on KRAS mutant status)
• 7/6/2012: FDA indication changed:
  • "indicated 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 based on KRAS mutant status)
  • Limitation of Use: Erbitux is not indicated for treatment of K-Ras mutation-positive colorectal cancer.

Head and neck cancer

• 3/1/2006: FDA indication expanded: (New disease entity)
  • in combination with radiation therapy, is indicated for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck.
  • as a single agent is indicated 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.
• 11/7/2011: FDA 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

Also known as

• Code name: C225
• Brand names: Cetuxim, Erbitux