Erbitux

Erbitux, in combination with radiation therapy, is a monoclonal antibody indicated for the initial treatment of locally or regionally advanced head and neck cancer of a specific type (squamous cell carcinoma).

Used alone, Erbitux is also approved to treat patients with head and neck cancers that have returned in the same location or spread to other parts of the body and for head and neck cancers that have progressed following platinum-based chemotherapy. Erbitux is also used on K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer as determined by an FDA-approved test.

• Erbitux can cause serious and fatal infusion reactions. Immediately interrupt and permanently discontinue Erbitux for serious infusion reactions.
• Cardiopulmonary arrest or sudden death occurred in patients with squamous cell carcinoma of the head and neck receiving Erbitux with radiation therapy or with a cetuximab product with platinum-based therapy and fluorouracil. Monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after Erbitux administration.

The most common side effects of Erbitux include:

• rash,
• itching,
• dry or cracked skin,
• nail changes,
• headache,
• diarrhea,
• nausea,
• vomiting,
• upset stomach,
• weight loss,
• weakness, and
• respiratory, skin, and mouth infections.

Erbitux also can cause low blood magnesium, potassium, and calcium. Patients taking Erbitux should limit their exposure to the sun. Rare but serious side effects of Erbitux include:

• life-threatening allergic reactions and
• heart attacks, especially if the patient was also obtaining chemotherapy or radiotherapy.

Patient Selection

Select patients with metastatic colorectal cancer (CRC) for treatment with Erbitux based on the presence of:

• Ras wild-type, EGFR-expressing CRC, or
• BRAF V600E mutation-positive metastatic CRC 

Information on FDA-approved tests for the detection of K-Ras or BRAF V600E mutations in CRC in patients with metastatic CRC is available at: https://www.fda.gov/CompanionDiagnostics.

Recommended Dosage for Squamous Cell Carcinoma of the Head and Neck (SCCHN)

In Combination with Radiation Therapy

• Initial dose: 400 mg/m² administered as a 120-minute intravenous infusion one week prior to initiating a course of radiation therapy.
• Subsequent doses: 250 mg/m² administered as a 60-minute infusion every week for the duration of radiation therapy (6-7 weeks).
• Complete Erbitux administration 1 hour prior to radiation therapy.

As A Single-Agent or in Combination with Platinum-Based Therapy and Fluorouracil

Administer Erbitux as a single-agent or in combination with platinum-based therapy and fluorouracil on a weekly or biweekly schedule.

Weekly Dosage

• Initial dose: 400 mg/m² administered as a 120-minute intravenous infusion
• Subsequent doses: 250 mg/m² administered as a 60-minute infusion every week

Biweekly Dosage

• Initial and subsequent doses: 500 mg/m² administered as a 120-minute intravenous infusion every 2 weeks

Complete Erbitux administration 1 hour prior to platinum-based therapy with fluorouracil. Continue treatment until disease progression or unacceptable toxicity.

Recommended Dosage for Colorectal Cancer (CRC)

As a single-agent or in combination with irinotecan or FOLFIRI (irinotecan, fluorouracil, leucovorin)

Administer Erbitux as a single-agent or in combination with irinotecan or FOLFIRI (irinotecan, fluorouracil, leucovorin) on a weekly or biweekly schedule.

Weekly Dosage

• Initial dose: 400 mg/m² administered as a 120-minute intravenous infusion
• Subsequent doses: 250 mg/m² administered as a 60-minute infusion every week

Biweekly Dosage

• Initial and subsequent doses: 500 mg/m² administered as a 120-minute intravenous infusion every 2 weeks

Complete Erbitux administration 1 hour prior to irinotecan or FOLFIRI. Continue treatment until disease progression or unacceptable toxicity

In Combination with Encorafenib

• The recommended initial dose is 400 mg/m² administered as a 120-minute intravenous infusion in combination with encorafenib.
• The recommended subsequent dosage is 250 mg/m² weekly as a 60-minute infusion in combination with encorafenib until disease progression or unacceptable toxicity.

Refer to the encorafenib prescribing information for recommended encorafenib dosage information.

Premedication

Premedicate with a histamine-1 (H₁) receptor antagonist intravenously 30-60 minutes prior to the first dose or subsequent doses as deemed necessary.

Dosage Modifications for Adverse Reactions

Reduce, delay, or discontinue Erbitux to manage adverse reactions as described in Table 1.

Table 1: Recommended Dosage Modifications for Adverse Reactions

There is no data available on drug interactions with Erbitux.

• Based on findings from animal studies and its mechanism of action, Erbitux can cause fetal harm when administered to a pregnant woman.
• There are no available data for Erbitux exposure in pregnancy.
• In an animal reproduction study, intravenous administration of cetuximab once weekly to pregnant cynomolgus monkeys during the period of organogenesis resulted in an increased incidence of embryolethality and abortion.
• Disruption or depletion of EGFR in animal models results in impairment of embryo-fetal development including effects on
  • placental,
  • lung,
  • cardiac,
  • skin, and
  • neural development.
• Human IgG is known to cross the placental barrier; therefore, cetuximab may be transmitted to the developing fetus.