Erbitux (cetuximab) - 2 indications

Scroll down for more information on each indication:

• for the treatment of metastatic colorectal cancer; approved February 2004
• for squamous cell carcinoma of the head and neck; approved November 2011

General Information

Erbitux (cetuximab) is a monoclonal antibody that targets and inhibits epidermal growth factor receptor (EGFr). 

Erbitux is specifically indicated for the following:

Head and Neck Cancer

• Locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy.
• Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with fluorouracil.
• Recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy. 

Colorectal Cancer

K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer as determined by an FDA-approved test:

• in combination with FOLFIRI for first-line treatment
• in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy
• as a single-agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan

Erbitux is supplied as an injection for intravenous administration. Scroll down for recommended dosing/administration for each indication.

Mechanism of Action

Erbitux is a recombinant, human/mouse chimeric monoclonal antibody. The antibody binds to epidermal growth factor receptor (EGFR, HER1, c-ErbB-1) on both normal and tumor cells, and competitively inhibits the binding of epidermal growth factor (EGF) and other ligands, such as transforming growth factor-alpha. It is composed of the Fv regions of a murine anti-EGFR antibody with human IgG1 heavy and kappa light chain constant regions.

Side Effects

Adverse reactions associated with Erbitux as a single-agent or in combination with radiotherapy or chemotherapy (FOLFIRI, Irinotecan and 5-Fluorouracil/Platinum) may include, but are not limited to, the following:

• cutaneous adverse reactions (including rash, pruritus, and nail changes)
• headache
• diarrhea
• infection

Adverse reactions associated with the use of Erbitux in combination with encorafenib may include, but are not limited to, the following:

• fatigue
• nausea
• diarrhea
• dermatitis acneiform
• abdominal pain
• decreased appetite
• arthralgia
• rash

The Erbitux drug label comes with the following Black Box Warning: 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.

Indication 1 - for the treatment of metastatic colorectal cancer

approved February 2004

Dosing/Administration

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.

Clinical Trial Results

FDA approval of Erbitux was based on three separate clinical trials on subjects with EGFR-expressing metastatic colorectal cancer, whose disease had progressed after receiving an irinotecan-containing regimen.

A randomized, controlled trial enrolling 329 subjects investigated Erbitux both as a monotherapy and in combination with irinotecan. Subjects received Erbitux plus irinotecan or Erbitux monotherapy, administered as a 400 mg/m2 initial dose, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicity. Eighty-eight percent of subjects had baseline Karnofsky Performance Status of 80 or higher. Fifty-eight percent of subjects had colon cancer and 40% rectal cancer with two-thirds of them having previously failed oxaliplatin treatment. Data showed that the median duration of response in the overall population was 5.7 months in the combination arm and 4.2 months in the monotherapy arm. Analysis showed that subjects randomized to Erbitux and irinotecan demonstrated a significantly longer median time to disease progression compared with Erbitux alone.

An open-label, single-arm trial enrolling 138 subjects investigated Erbitux in combination with irinotecan. Subjects received a 20-mg test dose of Erbitux on day 1, followed by a 400-mg/m2 initial dose, and 250 mg/m2 weekly until disease progression or unacceptable toxicity. Seventy-four subjects had documented progression to irinotecan. Results demonstrated an overall response rate of 15% for the overall population and 12% for the irinotecan-failure population. The median durations of response were 6.5 and 6.7 months, respectively.

In a third trial, Erbitux was studied as a single agent in a open-label, single-arm study enrolling 57 subjects. Results showed an overall response rate of 9% for the all-treated group and 14% for the irinotecan-failure group. The median times to progression were 1.4 and 1.3 months, respectively. The median duration of response was 4.2 months for both groups.

Indication 2 - for squamous cell carcinoma of the head and neck

approved November 2011

Dosing/Administration

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.

Clinical Trial Results

In Combination with Radiation Therapy (RT)

FDA approval was based on the phase 3 BONNER trial. The randomized, multicenter, controlled trial enrolled 424 patients with locally or regionally advanced SCCHN .Erbitux with RT increased median duration of locoregional control by 0.8 years vs RT alone (2.0 years vs 1.2 years, respectively). An OS advantage was maintained at 3 and 5 years. Erbitux with RT improved OS rate at 3 years vs RT alone; 55% vs 45%, respectively. 10% absolute improvement in 3-year survival rate vs RT alone. Erbitux with RT improved OS rate at 5 years vs RT alone; 45.6% vs 36.4%, respectively. 9.2% absolute improvement in 5-year survival rate vs RT alone.

In Combination with Platinum-based Therapy with Fluorouracil

FDA approval was based on EXTREME, an open-label, randomized, multicenter, controlled trial of 442 patients with recurrent locoregional disease or metastatic SCCHN. Patients received a cetuximab product in combination with platinum-based therapy and fluorouracil or platinum-based therapy and fluorouracil alone. The main efficacy outcome measure was OS. The median duration of OS in the Cetuximab with Platinum-based Therapy and Fluorouracil arm was 10.1 months versus 7.4 months in the Platinum-based Therapy and Fluorouracil arm. 

As Single-Agent

EMR 62202-016 was a single-arm, multicenter clinical trial in 103 patients with recurrent or metastatic SCCHN. All patients had documented disease progression within 30 days of a platinum-based chemotherapy regimen. Patients were administered intravenously a 20-mg test dose of Erbitux on Day 1, followed by a 400 mg/m2 initial dose, and 250 mg/m2 weekly until disease progression or unacceptable toxicity. The ORR was 13%. Median duration of response (DoR) was 5.8 months.