Cetuximab is a targeted biological therapy. Administered intravenously, it is often combined with other cancer treatments to enhance efficacy. It works by blocking a protein that promotes cancer cell growth, offering a more precise approach.
Cetuximab as a Targeted Cancer Therapy
Cetuximab is a monoclonal antibody, a laboratory-made protein that targets specific substances. It works by binding to the epidermal growth factor receptor (EGFR), a protein found on the surface of both healthy and cancerous cells. In many cancers, EGFR is overexpressed or altered, leading to uncontrolled cell growth and division.
Cetuximab attaches to the extracellular domain of EGFR, the part of the receptor that extends outside the cell. This binding prevents natural ligands, such as epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α), from activating the receptor. Blocking this activation inhibits downstream signaling pathways (e.g., Ras-Raf-MEK-ERK, PI3K-Akt) that promote cell proliferation, survival, and new blood vessel formation. This inhibition reduces cancer cell growth and can also trigger programmed cell death (apoptosis). Additionally, cetuximab can “tag” cancer cells for destruction by immune cells (e.g., natural killer cells) through antibody-dependent cellular cytotoxicity (ADCC).
Targeted therapy, unlike traditional chemotherapy, focuses on specific molecular pathways or proteins involved in cancer growth, often leading to fewer side effects on healthy cells. Chemotherapy typically uses strong chemicals to kill fast-growing cells, including both cancer cells and rapidly dividing healthy cells, which can result in broader systemic side effects.
Conditions Treated by Cetuximab
Cetuximab is used for treating specific types of cancer, primarily metastatic colorectal cancer (mCRC) and head and neck squamous cell carcinoma (HNSCC). For mCRC, it is generally used for tumors that express the EGFR protein and have a wild-type KRAS gene. It is often combined with chemotherapy regimens (e.g., FOLFIRI) as a first-line treatment.
For mCRC that has progressed after irinotecan-based chemotherapy, cetuximab can be used in combination with irinotecan. It may also be used as monotherapy if cancer did not respond to oxaliplatin and irinotecan-based chemotherapy or if irinotecan cannot be tolerated. It is also used in combination with encorafenib for mCRC with a BRAF V600E mutation.
For HNSCC, cetuximab is used in various settings. It is approved in combination with radiation therapy for initial treatment of locally or regionally advanced cancer. For recurrent or metastatic HNSCC, it can be combined with platinum-based chemotherapy and fluorouracil as a first-line treatment. It can also be used as a single agent for recurrent or metastatic HNSCC when prior platinum-based therapy has failed.
Potential Side Effects and Management
Cetuximab can cause a range of side effects, with dermatological issues common. An acne-like rash, which often appears on the face, neck, and upper torso, affects over 80% of patients. This rash, though uncomfortable, often suggests the medication is working. Management involves skin care, topical treatments, or dose adjustments. Other skin changes include dry skin, itching, scaling, hair growth alterations, and nail changes.
Infusion-related reactions can occur during or shortly after administration. Symptoms can include fever, chills, shortness of breath, and low blood pressure. To reduce these reactions, patients often receive pre-medications like antihistamines and corticosteroids. If a reaction occurs, the infusion may be slowed or temporarily stopped.
Gastrointestinal issues, such as nausea, vomiting, and diarrhea, are also reported. These are managed with anti-nausea medications and adequate hydration. Temporary adjustments to the cetuximab dosage may be necessary. Cetuximab can also lead to electrolyte imbalances, particularly low magnesium, potassium, and calcium. Regular blood tests monitor these levels, and supplements may be prescribed to maintain balance and prevent complications like muscle cramps or fatigue.
Important Patient Considerations
Biomarker testing is important before starting cetuximab, especially for patients with metastatic colorectal cancer. Testing for KRAS, NRAS, and BRAF gene mutations is performed because they can indicate a lack of response to cetuximab. For instance, if a tumor has a KRAS mutation in exons 2, 3, or 4, or an NRAS mutation in exons 2, 3, or 4, cetuximab treatment is generally not recommended, as patients are unlikely to benefit. While BRAF V600E mutations suggest a low likelihood of response to cetuximab alone, it can be used in combination with a BRAF inhibitor like encorafenib. For head and neck squamous cell carcinoma, RAS mutations are less frequent, and routine biomarker testing for cetuximab efficacy is not as clearly established.
It is administered as an intravenous infusion, typically on a weekly or bi-weekly schedule. The initial dose is infused over about 120 minutes, with subsequent doses taking about 60 minutes. Patients are monitored throughout treatment with regular blood tests to check for electrolyte imbalances and assess overall progress. The duration of treatment varies by cancer type and individual patient response, continuing until disease progression or unacceptable side effects.