Histological differentiation of skin toxicity between cetuximab, erlotinib and panitumumab (single ErbB1) and lapatinib (dual ErbB1/2) epidermal growth factor receptor inhibitors

Abstract

e20617 Background: Epidermal growth factor receptor inhibition by monoclonal antibodies and tyrosine kinase inhibitors has demonstrated activity in solid tumors. However, blockade of EGFR in skin results in disabling skin toxicity that may lead to therapeutic dose modification or interruption. This study compares cutaneous histological alterations among four EGFR inhibitors (EGFRIs): cetuximab (C), erlotinib (E), lapatinib (L) and panitumumab (P). Methods: Punch skin biopsies from patients with papulopustular rash were collected from 8 patients per each EGFRI (n=32). Two dermatopathologists performed independent blinded assessment of epidermis, dermis, follicle and inflammatory infiltrates. Histologic features were rated as 0 (absent) or 1 (present), with the exception of dyskeratosis, rated from 0 (absent) to 2 (severe) and infiltrate, rated from 0 (absent) to 3 (most prominent). Where variation occurred, scores were reconciled and combined for analysis. Results: Epidermal atrophy was observed for C, E, L and P (range 0–1, median 1, 1, 0, 0.5, respectively) and neutrophilic follicular infiltrate was observed for C, E, L and P (range 0–3, median 0.5, 3, 0, 3, respectively). Neutrophilic dermal infiltrate (range 0–3) and follicular neutrophilic pustules (range 0–1) were most prevalent in P (median 0.5), whereas the median for C, E and L was 0. A mononuclear dermal infiltrate (range 0–3) was least prevalent with C (median 0) while E, L and P had a median of 0.5. Concretions (range 0–1) were most prevalent for E (median 1), whereas the median for C, L and P was 0. Conclusions: Lapatinib, a dual ErbB1/2 inhibitor, induced the least structural disarray and inflammation in the skin as measured by median scores for epidermal atrophy, neutrophilic dermal and follicular infiltrates, neutrophilic pustules and lack of bacterial concretions. These histological data confirm a more benign pattern of rash with lapatinib compared to single ErbB1 inhibitors. [Table: see text]