Frontiers in pharmacology · 2026
Pharmacovigilance analysis of cutaneous adverse drug reactions for cetuximab, panitumumab, and necitumumab based on EudraVigilance and WHO VigiAccess.
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Sauer Natalia, Giedziun Piotr, Calik Jacek, Wiela-Hojeńska Anna
Аннотация
INTRODUCTION: Anti-EGFR monoclonal antibodies (mAbs)--cetuximab, panitumumab, and necitumumab--are cornerstone therapies for selected solid tumors but are frequently associated with cutaneous adverse drug reactions (ADRs). This study aimed to characterize and compare the dermatologic safety profiles of these agents using large-scale post-marketing pharmacovigilance data.
METHODS: A comprehensive pharmacovigilance analysis was conducted using aggregated ADR reports from the WHO VigiAccess and European Medicines Agency (EMA) EudraVigilance databases. Disproportionality analyses were performed using reporting odds ratios (RORs) and proportional reporting ratios (PRRs). Dermatologic ADR diversity and similarity were further evaluated using Shannon entropy, principal component analysis (PCA), and multidimensional scaling (MDS).
RESULTS: A total of 50,391, 18,806, and 355 ADR reports were identified for cetuximab, panitumumab, and necitumumab, respectively. Cutaneous ADRs accounted for up to 25% of all reported events. Panitumumab demonstrated the strongest association with skin-related toxicities (ROR = 1.51; PRR = 1.38), particularly acneiform dermatitis, pruritus, and xerosis. Cetuximab exhibited lower relative disproportionality despite higher absolute numbers of reported cases, whereas necitumumab showed a narrower dermatologic toxicity profile, potentially reflecting lower utilization or underreporting. Shannon entropy and dimensionality reduction analyses revealed greater heterogeneity of dermatologic ADRs associated with panitumumab compared with cetuximab and necitumumab. Significant differences in ADR distributions were observed between the WHO and EMA databases.
DISCUSSION: These findings highlight distinct agent-specific dermatologic toxicity signatures among anti-EGFR monoclonal antibodies and demonstrate the value of real-world pharmacovigilance data in complementing clinical trial evidence. Improved recognition of differential toxicity patterns may support personalized monitoring and management strategies for patients receiving EGFR-targeted therapies.
METHODS: A comprehensive pharmacovigilance analysis was conducted using aggregated ADR reports from the WHO VigiAccess and European Medicines Agency (EMA) EudraVigilance databases. Disproportionality analyses were performed using reporting odds ratios (RORs) and proportional reporting ratios (PRRs). Dermatologic ADR diversity and similarity were further evaluated using Shannon entropy, principal component analysis (PCA), and multidimensional scaling (MDS).
RESULTS: A total of 50,391, 18,806, and 355 ADR reports were identified for cetuximab, panitumumab, and necitumumab, respectively. Cutaneous ADRs accounted for up to 25% of all reported events. Panitumumab demonstrated the strongest association with skin-related toxicities (ROR = 1.51; PRR = 1.38), particularly acneiform dermatitis, pruritus, and xerosis. Cetuximab exhibited lower relative disproportionality despite higher absolute numbers of reported cases, whereas necitumumab showed a narrower dermatologic toxicity profile, potentially reflecting lower utilization or underreporting. Shannon entropy and dimensionality reduction analyses revealed greater heterogeneity of dermatologic ADRs associated with panitumumab compared with cetuximab and necitumumab. Significant differences in ADR distributions were observed between the WHO and EMA databases.
DISCUSSION: These findings highlight distinct agent-specific dermatologic toxicity signatures among anti-EGFR monoclonal antibodies and demonstrate the value of real-world pharmacovigilance data in complementing clinical trial evidence. Improved recognition of differential toxicity patterns may support personalized monitoring and management strategies for patients receiving EGFR-targeted therapies.