Epidermal Growth Factor Receptor Inhibitors: Cutaneous Side Effects and Their Management

Seena Monjazeb, MD; Janice Wilson, MD; Brent Kelly, MD


Skin Therapy Letter. 2017;22(5):5-7. 

In This Article

Abstract and Introduction


Epidermal growth factor receptor (EGFR) inhibitors are part of an emerging class of anticancer medicines known as "targeted therapy," which target pathways more specific to neoplastic proliferation than traditional chemotherapeutic agents. Adverse effects of such treatments are thought to be less severe, but can still be significant. Because EGFR is preferentially expressed in epithelial tissues, including the skin and hair follicle, cutaneous side effects of these agents are quite common. Not only can these toxicities severely affect patients' quality of life, but in some specific instances, they can be associated with increased response to therapy. It is of paramount importance that clinicians familiarize themselves with and understand the basic management of the range of cutaneous adverse effects caused by these drugs.


The epidermal growth factor receptor (EGFR) is expressed in epithelial tissues as well as hair follicles. It contributes to epidermal proliferation, differentiation, and hair growth. Upregulating mutations of EGFR have been found in many solid tumors.[1] The discovery of EGFR's role as an oncogene has led to the development of many new inhibitors for the treatment of various neoplasms of the head, neck, colon, and lung. These drugs have been shown to increase the rate of response to treatment, delaying disease progression and improving quality of life. Standard chemotherapeutic agents nonspecifically affect cells that proliferate rapidly; in contrast, EGFR inhibitors (EGFRIs) target pathways more specific to survival of neoplastic cells, thus belonging to a new class of chemotherapeutic agents - so-called "targeted therapy." These targeted therapies are usually associated with fewer systemic side effects than standard chemotherapy.[2]

There are several different types of EGFRIs, including small molecule tyrosine kinase inhibitors, monoclonal antibodies, and multikinase inhibitors. Small molecule tyrosine kinase inhibitors, such as gefitinib and erlotinib, selectively bind the adenosine triphosphate (ATP)-binding site of the EGFR tyrosine kinase receptor, inhibiting the receptor's intracellular domain via preventing phosphorylation.[3,4] Both gefitinib and erlotinib are approved for the treatment of non-small cell lung cancer, and erlotinib in combination with gemcitabine is approved for the treatment of advanced pancreatic cancer.

In contrast, monoclonal antibodies that target EGFR, such as cetuximab and panitumumab, bind to its extracellular domain and competitively inhibit endogenous ligand binding to the receptor.[3,4] These antibodies are approved for the treatment of advanced EGFR-expressing colorectal cancer, and cetuximab is also approved for treatment of squamous cell carcinoma of the head and neck. There are also combination therapies that affect multiple receptors such as lapatinib (approved for human epidermal growth factor receptor 2-positive [HER2+] breast cancer) and afatinib (approved for non-small cell lung cancer), which inhibit both the EGFR and HER2 receptors, and vandetanib (approved for advanced medullary thyroid cancer), which inhibits EGFR, vascular endothelial growth factor (VEGFR), and rearranged during transfection (RET) activities.

Although these drugs have been proven to be very effective for normally untreatable advanced neoplasms, EGFRIs cause cutaneous side effects in 50% or more of patients undergoing treatment.[1] The most common of these adverse reactions include acneiform eruptions, paronychia, xerosis, mucositis, and alopecia, and less common side effects include trichomegaly, hirsutism, and hyperpigmentation. The occurrence of some EGFRIassociated cutaneous toxicities is actually associated with clinical response to the medication. However, cutaneous side effects can result in decreased quality of life and may cause interruption or discontinuation of therapy despite effectiveness.[3] Therefore, it is important to understand the cutaneous side effects of EGFRIs and their management in order to improve quality of life, increase compliance and avoid unnecessary interruption or cessation of treatment.