Supplementary Material for: Skin barrier dysfunction, antimicrobial peptide alterations, and microbiome changes in solid cancer patients treated with epidermal growth factor receptor inhibitors

Background: Epidermal growth factor receptor inhibitors (EGFRI) are targeted therapies for solid cancers. Its use is associated with cutaneous adverse events (cAEs).
Objectives: To investigate the occurrence of cAEs and changes in skin biophysical properties reflecting the skin barrier function, alterations in antimicrobial peptides (AMP) and the skin microbiome, in patients undergoing treatment with EGFRI.
Methods: A two-year prospective cohort study was conducted involving patients receiving EGFRI for solid cancers. cAEs and skin biophysical properties, including transepidermal water loss (TEWL), skin pH, elasticity, sebum, and pigmentation, were measured at baseline and follow-up visits up to 48 weeks. AMP were assessed using a tape-stripping technique from the cheeks at months 0, 1, and 6, with protein assays and ELISA to determine the levels of human beta-defensin (hBD)-3 and ribonuclease (RNase)-7. Skin microbiome analysis was performed through 16S rRNA sequencing of cheek swabs collected at months 0, 1, and 6.
Results: Eighty-four patients were enrolled. The cumulative incidence of cAEs was 94.05%. Skin biophysical properties showed significantly increased TEWL and pH, decreased pigmentation, and no significant changes in elasticity and sebum. AMP analysis from 15 patients revealed significant reduction of RNase-7 levels after 6 months into EGFRI, while hBD-3 levels change was insignificant. Microbiome study from eighteen patients showed statistically increased Corynebacterium kroppenstedtii at months 1 and 6, while Cutibacterium acnes, Corynebacterium aurimucosum, Staphylococcus epidermidis, and Staphylococcus aureus were not significantly different among groups.
Conclusions: Treatment with EGFRI compromises skin barrier function and AMP production, leading to skin microbiota changes.