ERBITUX

What it is

Erbitux (cetuximab (rmc)) is a solution for injection administered by intravenous infusion. Each 20 mL vial contains 100 mg cetuximab, and each 100 mL vial contains 500 mg cetuximab. Erbitux is a sterile, preservative-free, clear to slightly opalescent, colourless to yellowish solution that is intended for intravenous infusion. Cetuximab is an antineoplastic monoclonal antibody. Cetuximab is a chimaeric monoclonal antibody of the immunoglobulin G1 subclass, produced in mammalian cell culture. It is obtained by attaching the variable regions of the murine monoclonal antibody M225 against epidermal growth factor receptor (EGFR) to constant regions of the human IgG1.

Approved indications —

Metastatic colorectal cancer in combination with infusional 5-fluorouracil/folinic acid plus irinotecan — Metastatic colorectal cancer in combination with irinotecan in patients who are refractory to first-line chemotherapy — Metastatic colorectal cancer in first-line in combination with FOLFOX — Metastatic colorectal cancer as a single agent in patients who have failed or are intolerant to oxaliplatin-based therapy and irinotecan-based therapy — Squamous cell cancer of the head and neck in combination with radiation therapy for locally advanced disease — Squamous cell cancer of the head and neck in combination with platinum-based chemotherapy for recurrent and/or metastatic disease

Dosing overview

Detection of RAS mutational status (K-RAS and N-RAS exons 2, 3 and 4) must be performed prior to the first cetuximab infusion. For metastatic colorectal cancer, the initial dose is 400 mg cetuximab per m² body surface area with a recommended infusion period of 120 minutes. All subsequent weekly doses are 250 mg/m² each with a recommended infusion period of 60 minutes. Alternatively, Erbitux may be administered once every two weeks at 500 mg cetuximab per m² body surface area with a recommended infusion period of 120 minutes. For squamous cell cancer of the head and neck in combination with radiation therapy, the initial dose is 400 mg cetuximab per m² body surface area with a recommended infusion period of 120 minutes. All subsequent weekly doses are 250 mg/m² each with a recommended infusion period of 60 minutes. For squamous cell cancer of the head and neck in combination with platinum-based chemotherapy, the initial dose is 400 mg cetuximab per m² body surface area with a recommended infusion period of 120 minutes. All subsequent weekly doses are 250 mg/m² each with a recommended infusion period of 60 minutes. Alternatively, Erbitux may be administered once every two weeks at 500 mg cetuximab per m² body surface area with a recommended infusion period of 120 minutes.

Key safety warnings

Prior to the first infusion, patients must receive premedication with an antihistamine and a corticosteroid at least 1 hour prior to administration of cetuximab. Similar premedication is recommended for all subsequent infusions. Close monitoring is required during the infusion and for at least 1 hour after the end of the infusion. Availability of resuscitation equipment must be ensured. Severe infusion-related reactions, including anaphylactic reactions, may commonly occur, in some cases with fatal outcome. Occurrence of a severe infusion-related reaction requires immediate and permanent discontinuation of cetuximab therapy and may necessitate emergency treatment. The risk for anaphylactic reactions is much increased in patients with a history of allergy to red meat or tick bites or positive results of tests for IgE antibodies against cetuximab (α-1-3-galactose). In these patients cetuximab should be administered only after a careful assessment of benefit/risk, including alternative treatments, and only under close supervision of well trained personnel with resuscitation equipment ready. Cases of interstitial lung disease (ILD), including fatal cases, have been reported, with the majority of cases arising from a Japanese postmarketing surveillance study in metastatic colorectal cancer. Confounding or contributing factors, such as concomitant chemotherapy known to be associated with ILD, and pre-existing pulmonary diseases were frequent in fatal cases. Such patients should be closely monitored. Progressively decreasing serum magnesium levels occur frequently and may lead to severe hypomagnesaemia. Hypomagnesaemia is reversible following discontinuation of cetuximab. Measurement of serum electrolyte levels is recommended prior to and periodically during cetuximab treatment. Electrolyte replacement is recommended, as appropriate. Skin reactions may develop in more than 80% of patients and mainly present as acne-like rash and/or, less frequently, as pruritus, dry skin, desquamation, hypertrichosis, or nail disorders (e.g. paronychia). Approximately 15% of the skin reactions are severe, including single cases of skin necrosis.

Contraindications

Erbitux is contraindicated in patients with known severe (grade 3 or 4) hypersensitivity reactions to cetuximab. The combination of Erbitux with oxaliplatin-containing chemotherapy is contraindicated for patients with mutant RAS metastatic colorectal cancer (mCRC) or for whom RAS mCRC status is unknown.

PBS listing

The 100 mg in 20 mL solution for intravenous infusion strength is listed on the PBS with 14 items under streamlined restriction at an ex-manufacturer price of A$268.53.

Regulatory history

Erbitux was first registered on the ARTG on 25 September 2007 with two registered strengths: 100 mg in 20 mL and 500 mg in 100 mL solution for intravenous infusion. An AusPAR was approved on 14 May 2013, leading to a revised therapeutic use for Erbitux covering the treatment of EGFR-expressing, K-RAS wild-type metastatic colorectal cancer. In March 2018, the PBAC recommended Erbitux for recurrent or metastatic squamous cell carcinoma of the head and neck under Section 100 listing. In November 2021, this recommendation was withdrawn and rescinded by the PBAC with support from the sponsor. In March 2024, the PBAC recommended Erbitux for metastatic colorectal cancer (mCRC).