Severe scarring alopecia associated with combinational use of ficlatuzumab and gefitinib: a clinical and immunohistochemistry study

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, are among the standard treatments for patients of non-small cell lung cancer (NSCLC). However, EGFR TKI resistance is commonly encountered after prolonged treatment. Hepatocyte growth factor (HGF) is the soluble ligand for the c-Met tyrosine kinase receptor, which is normally expressed by epithelial cells, frequently overexpressed in NSCLC, and contributed to EGFR TKI resistance. Thus, an anti-hepatocyte growth factor monoclonal antibody, ficlatuzumab (AV-299), is introduced to be used in combination with gefitinib in a phase 2 study conducted among Asian patients with NSCLC.

We observed severe refractory scarring alopecia in patients using the above-mentioned combination. Although severe scalp inflammation with hair loss presenting as scarring or non-scarring alopecia associated with single use of gefitinib or erlotinib has been reported, our cases represented the most severe scarring variant, including a case of folliculitis decalvans, and the most rapid-onset variant of this scalp side effect. HGF and EGF both played parts in Stat3-dependent hair cycle induction. We hypothesized that simultaneous inhibition of HGF and EGF by combinational use of ficlatuzumab and gefitinib may lead to a synergistic toxicity presenting as more severe scarring hair loss. Besides the clinical significance, the expression and localization of EGFR and c-Met tyrosine kinase receptor in hair follicles have not been well studied. In this study, we present the clinical and immunohistochemistry features in both normal human hair follicles and in hair follicles from patients receiving combinational use of ficlatuzumab and gefitinib.