Meta-analysis of Incidence of Infusion Reactions to Anti-EGFR Antibodies in Patients with mCRC
The application of antibodies against the epidermal growth factor receptor (EGFR), administered in slow infusions mainly as part of the treatment for metastatic colorectal cancer (mCRC), may be accompanied by infusion reactions or hypersensitivity reactions.
Infusion Reactions
Most intravenously administered oncology drugs have the potential to cause infusion reactions. These reactions can be mediated either by IgE (allergic reaction, type 1 hypersensitivity) or by other mechanisms (anaphylactoid, non-allergic reaction). The severity of these reactions can vary greatly, as can their occurrence—while platinum-based drugs, for example, usually cause reactions after 6–8 administrations, antibodies typically cause reactions during the first or second infusion. Anaphylaxis manifests within minutes of starting the drug application, whereas cytokine release symptoms typically appear after 30–120 minutes.
Early signs of infusion reactions include respiratory or cardiac symptoms, characteristic skin changes, confusion, dizziness, anxiety, arthralgia, fever, nausea, and vomiting. Infusion reactions are relatively less common with anti-EGFR antibodies compared to other drugs, but the incidence is inconsistently reported between 0 and 33%, with a higher frequency for cetuximab compared to panitumumab.
Systematic Review and Meta-Analysis
A recent systematic review and meta-analysis by a team of American authors includes observational or clinical studies of patients with mCRC treated with anti-EGFR antibodies that reported the occurrence of infusion reactions, hypersensitivity, or allergy/anaphylaxis. The aim of the meta-analysis was to estimate the incidence of infusion reactions. A random effects model was used for the calculation, which also applied to stratifying the incidence by type of therapy, study design, geographical location, RAS or KRAS oncogene mutation status, severity of reactions, and terminology used to describe the reaction.
Results
The estimated incidence of infusion reactions was found to be 4.9% (95% confidence interval [CI] 3.6–6.5%). Less severe reactions were generally more common than more severe reactions. The incidence of reactions to cetuximab was almost four times higher than for panitumumab (6.1% vs. 1.6%).
Conclusion
Infusion reactions occur in approximately 5% of patients with mCRC treated with anti-EGFR antibodies. The incidence significantly differs between individual drugs, as does the severity of the reactions. A higher rate of incidence was observed with cetuximab, while panitumumab demonstrated a more favorable safety profile in this regard.
The authors of the analysis further found that higher incidences of reactions were reported in studies with smaller patient numbers, whereas studies with larger patient cohorts showed lower incidences of infusion reactions. Studies evaluating these aspects of oncology treatment should consider the relationship between treatment efficacy and patient prognosis and the occurrence of infusion reactions to determine the prognostic relevance of the incidence and severity of these reactions.
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Source: Bylsma L. C., Dean R., Lowe K. et al. 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. Cancer Med 2019; 8 (12): 5800–5809, doi: 10.1002/cam4.2413.
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