Abstract 429P
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.
Resources from the same session
465P - A phase IIIb open-label study of afatinib in EGFR TKI-naïve patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC: Exploratory biomarker analysis
Presenter: Jie Wang
Session: Poster display session
Resources:
Abstract
470P - Prognostic significance of serum biomarkers in small cell lung cancer: A meta-analysis and systematic review
Presenter: Rogelio Velasco
Session: Poster display session
Resources:
Abstract
471P - Chemotherapy in advanced thymic malignancies
Presenter: Ankur Varshney
Session: Poster display session
Resources:
Abstract
466P - Cancer immunotherapy efficacy and patients’ age: A systematic review and meta-analysis
Presenter: Yu Jiang
Session: Poster display session
Resources:
Abstract
506P - Efficacy and safety of pegvorhyaluronidase alfa (PEGPH20; PVHA) and pembrolizumab (pembro) combination therapy in patients (Pts) with stage III/IV non-small cell lung cancer (NSCLC)
Presenter: Jeffrey Ward
Session: Poster display session
Resources:
Abstract
480P - Safety and efficacy of dacomitinib for EGFR+ NSCLC in the subgroup of Asian patients from ARCHER 1050
Presenter: Tony S.K. Mok
Session: Poster display session
Resources:
Abstract
503P - Activity of afatinib in patients (pts) with NSCLC harboring uncommon EGFR mutations: Pooled analysis of three large phase IIIB trials
Presenter: Antonio Passaro
Session: Poster display session
Resources:
Abstract
488P - Randomized trial of prophylactic minocycline for erlotinib-associated skin rash in non-small cell lung cancer (PEARL trial)
Presenter: Kei Kusaka
Session: Poster display session
Resources:
Abstract
495P - Tracking of activating EGFR mutations predicts progression-free survival in advanced EGFR-mutated NSCLC patients treated with osimertinib
Presenter: Anna Buder
Session: Poster display session
Resources:
Abstract
520P - A phase II study to evaluate abscopal effect by palliative radiation therapy in nivolumab treatment for pretreated non-small cell lung cancer (HANSHIN 0116)
Presenter: Akito Hata
Session: Poster display session
Resources:
Abstract