429P - Skin pathologic change evaluation of the patients who had EGFR inhibitor-related skin adverse events

Background

Epidermal growth factor receptor (EGFR) inhibitors are a standard treatment for various malignant tumors, especially in colon cancer and lung cancer. The most common adverse reaction of EGFR inhibitors is skin toxicity, including acneiform rash, xerosis, paronychial inflammation, pruritus, photosensitivity, and hair/eyelash alterations. Even though EGFR inhibitor-related skin adverse events (ERSEs) are predictive marker of EGFR inhibitors treatment survivals, those are frequently also the reason for premature termination of anti-EGFR therapy. It is therefore important to understand the mechanisms underlying the skin toxicities caused by EGFR inhibition to improve anti-EGFR–based cancer therapies and minimize debilitating side effects for patients.

Methods

Twelve patients’ ERSEs skin biopsies which were treated with EGFR inhibitors were compared to same numbers of controlled skin biopsies those who did not use EGFR inhibitors. We evaluated Ki-67, EGFR, Melan-A, interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α) expression based on immunohistochemical (IHC) stains between 2 groups. Among them, five patients were treated with EGF ointment for ERSE. We also observed skin changes before and after EGF ointment.

Results

Control and ERSE group’s Ki-67 expression of epidermis were 40.8% vs 21.2% (P = 0.015). EGFR presentation range of epidermis was 98.3% vs 84.6% in control and ERSEs group, respectively (P = 0.001). We could observe 14.2% vs 8.1% (P = 0.069) of Melan-A IHC stain. In the IL-17, ERSE group’s IL-17 expression intensity (16.1) was higher than control group (9.8) (P = 0.038). Much higher TNF-α expression intensity (13.3) was also observed in ERSE group compared control group (7.9) (P = 0.037). After treatment with EGF ointment of 5 patients, values of Ki-67, EGFR, Melan-A, IL-17, and TNF-α were changed to 28%, 94%, 8.2%, 12.5 and 10, respectively.

Conclusions

Treatment with EGFR inhibitors decreased expression of Ki-67 and EGFR in the patients’ dermis. This seems to lead to secondary inflammation of the skin. The treatment of EGF ointment for ERSEs is thought to normalize EGFR level and the inflammatory response to some extent.

Clinical trial identification

NCT02284139.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Daewoong Pharmaceutical Company.

Disclosure

J.M. Kim: Full / Part-time employment: Daewoong pharmacy. J.E. Choo: Full / Part-time employment: Daewoong pharmacy. All other authors have declared no conflicts of interest.