The following adverse reactions are discussed in greater detail in other sections of the label:

• Infusion reactions [See BOXED WARNING and Warnings and PRECAUTIONS.]
• Cardiopulmonary arrest [See BOXED WARNING and Warnings and PRECAUTIONS.]
• Pulmonary toxicity [See Warnings and PRECAUTIONS.]
• Dermatologic toxicity [See Warnings and PRECAUTIONS.]
• Hypomagnesemia and Electrolyte Abnormalities [See Warnings and PRECAUTIONS.]

The most common adverse reactions with Erbitux® (incidence ≥ 25%) are cutaneous adverse reactions (including rash, pruritus, and nail changes), headache, diarrhea, and infection.

The most serious adverse reactions with Erbitux® are infusion reactions, cardiopulmonary arrest, dermatologic toxicity and radiation dermatitis, sepsis, renal failure, interstitial lung disease, and pulmonary embolus.

Across all studies, Erbitux® was discontinued in 3-10% of patients because of adverse reactions.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data below reflect exposure to Erbitux® in 1373 patients with colorectal cancer or SCCHN in randomized phase 3 (Studies 1 and 3) or phase 2 (Studies 2 and 4) trials treated at the recommended dose and schedule for a median of 7 to 14 weeks. [See Clinical Studies.]

Infusion reactions: Infusion reactions, which included pyrexia, chills, rigors, dyspnea, bronchospasm, angioedema, urticaria, hypertension, and hypotension occurred in 15- 21% of patients across studies. Grades 3 and 4 infusion reactions occurred in 2-5% of patients; infusion reactions were fatal in 1 patient.

Infections: The incidence of infection was variable across studies, ranging from 13-35%. Sepsis occurred in 1-4% of patients.

Renal: Renal failure occurred in 1% of patients with colorectal cancer.

Squamous Cell Carcinoma of the Head and Neck

Table 2 contains selected adverse events in 420 patients receiving radiation therapy either alone or with Erbitux® for locally or regionally advanced SCCHN in Study 1. Erbitux® was administered at the recommended dose and schedule (400 mg/m² initial dose, followed by 250 mg/m² weekly). Patients received a median of 8 infusions (range 1-11).

Table 2:Incidence of Selected Adverse Events ( ≥ 10%) in Patients with Locoregionally Advanced SCCHN

The incidence and severity of mucositis, stomatitis, and xerostomia were similar in both arms of the study.

Late Radiation Toxicity

The overall incidence of late radiation toxicities (any grade) was higher in Erbitux® in combination with radiation therapy compared with radiation therapy alone. The following sites were affected: salivary glands (65% versus 56%), larynx (52% versus 36%), subcutaneous tissue (49% versus 45%), mucous membrane (48% versus 39%), esophagus (44% versus 35%), skin (42% versus 33%). The incidence of Grade 3 or 4 late radiation toxicities was similar between the radiation therapy alone and the Erbitux® plus radiation treatment groups.

Colorectal Cancer

Table 3 contains selected adverse events in 562 patients receiving best supportive care (BSC) alone or with Erbitux® monotherapy for metastatic colorectal cancer in Study 3. Erbitux® was administered at the recommended dose and schedule (400 mg/m² initial dose, followed by 250 mg/m² weekly).

Table 3: Incidence of Selected Adverse Events Occurring in ≥ 10% of Patients with Advanced Colorectal Carcinoma¹ Treated with Erbitux® Monotherapy

The most frequently reported adverse events in 354 patients treated with Erbitux® plus irinotecan in clinical trials were acneform rash (88%), asthenia/malaise (73%), diarrhea (72%), and nausea (55%). The most common Grade 3/4 adverse events included diarrhea (22%), leukopenia (17%), asthenia/malaise (16%), and acneform rash (14%).

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. Immunogenic responses to cetuximab were assessed using either a double antigen radiometric assay or an ELISA assay. Due to limitations in assay performance and sampling timing, the incidence of antibody development in patients receiving Erbitux® has not been adequately determined. Non-neutralizing anti-cetuximab antibodies were detected in 5% (49 of 1001) of evaluable patients without apparent effect on the safety or antitumor activity of Erbitux®.

The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Erbitux® with the incidence of antibodies to other products may be misleading.

A drug interaction study was performed in which Erbitux® was administered in combination with irinotecan. There was no evidence of any pharmacokinetic interactions between Erbitux® and irinotecan.

Bookmark this page: