The incidence of infusion reactions associated with monoclonal antibody drugs targeting the epidermal growth factor receptor in metastatic colorectal cancer patients: A systematic literature review and meta‐analysis of patient and study characteristics

Abstract

Background Systemic cancer therapies may induce infusion reactions (IRs) or hypersensitivities. Metastatic colorectal cancer (mCRC) patients treated with anti‐EGFR therapies, including cetuximab and panitumumab, may be subject to these reactions. We conducted a meta‐analysis to estimate the IR incidence in this population and identify variations in this incidence by patient or study characteristics. Methods A systematic review was conducted to identify observational studies or clinical trials of mCRC patients treated with anti‐EGFR therapies that reported occurrences of IRs, hypersensitivity, or allergy/anaphylaxis. The objective of the study was to estimate the incidence of IRs. Random effects models were used to meta‐analyze the incidence of IRs overall and stratified by therapy type, study design, geographic location, RAS or KRAS mutation status, grade of reaction severity, and terminology used to describe the reaction. Results The pooled estimate for IR incidence was 4.9% (95% confidence interval: 3.6%‐6.5%). Lower‐grade reactions were more common than higher‐grade reactions overall and the incidence of reactions among cetuximab patients was nearly four times that of panitumumab patients (6.1% vs 1.6%). Conclusions IRs occur in approximately 5% of mCRC patients treated with anti‐EGFR therapies, and the incidence varies significantly by grade of severity and therapy type. Studies evaluating these outcomes should consider investigating survival outcomes by IR status to determine its prognostic relevance.

Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization

“…The incidence of IDHRs in Cetuximab is estimated at 3%. This mAb can induce anaphylaxis during the first exposure due to the presence of preexisting IgE antibodies against galactose-α-1,3-galactose, a oligosaccharide expressed in the Fab portion of cetuximab [55][56][57].…”

Biweekly cetuximab in combination with capecitabine and oxaliplatin (XELOX) or irinotecan (XELIRI) in the first-line and second-line treatment of patients with RAS wild-type metastatic colorectal cancer

“…In a meta-analysis of 47 studies, the rate of infusion reactions in patients treated with cetuximab was 6% compared to 1.6% with the human monoclonal antibody anti-EGFR panitumumab [ 54 ]. We found only one patient (1.6%) with documented infusion reaction (grade 3).…”

Systemic Therapy for Metastatic Colon Cancer: New Frontiers

“…Due to the chimeric nature of cetuximab, it is associated with severe infusion reactions in approximately 5% of patients. 14 The fully human antibody (IgG2) against EGFR (panitumumab) was developed by immunization of transgenic mice and is associated with a <1% risk of severe infusion reactions. 12,14 The mechanism of action of panitumumab is similar to cetuximab, and when given as monotherapy it had a response rate of 8% in patients with chemotherapy-refractory metastatic colorectal cancer.…”

“…14 The fully human antibody (IgG2) against EGFR (panitumumab) was developed by immunization of transgenic mice and is associated with a <1% risk of severe infusion reactions. 12,14 The mechanism of action of panitumumab is similar to cetuximab, and when given as monotherapy it had a response rate of 8% in patients with chemotherapy-refractory metastatic colorectal cancer. 15 Panitumumab gained accelerated U.S. Food and Drug Administration (FDA) approval in 2008.…”