Dermatologic Toxicity Occurring During Anti-EGFR Monoclonal Inhibitor Therapy in Patients With Metastatic Colorectal Cancer: A Systematic Review

Abstract

Monoclonal antibody inhibitors of the epidermal growth factor receptor (EGFR) have been shown to improve outcomes for patients with metastatic colorectal cancer (mCRC) without RAS gene mutations. However, treatment with anti-EGFR agents can be associated with toxicities of the skin, nails, hair, and eyes. Because these dermatologic toxicities can result in treatment discontinuation and affect patient quality of life, their management is an important focus when administering anti-EGFR monoclonal antibodies. The present systematic review describes the current data reporting the nature and incidence of, and management and treatment options for, dermatologic toxicities occurring during anti-EGFR treatment of mCRC. A search of the National Library of Medicine PubMed database from January 1, 2009, to August 18, 2016, identified relevant reports discussing dermatologic toxicity management among patients with mCRC receiving anti-EGFR therapy. The studies were grouped by type and rated by level of evidence using the GRADE approach developed by the Agency for Healthcare Research and Quality. Overall, 269 reports were reviewed (nonrandomized trials, n = 120; randomized trials, n = 31; retrospective studies, n = 15; reviews, n = 39). Dermatologic toxicity of any grade occurs in most patients who receive anti-EGFR therapy; approximately 10% to 20% of patients experienced grade 3/4 toxicity. The most common dermatologic toxicities include papulopustular/acneiform rash, xerosis, and pruritus; however, nail changes, hair abnormalities, and ocular conditions also occur. Guidance for managing these toxicities includes the use of inexpensive emollient ointments and moisturizers, avoidance of sun exposure, avoidance of irritants, and the use of short showers. Several studies also found that preemptive treatment was more effective than reactive treatment at limiting the incidence and severity of skin toxicity. With appropriate treatment, the dermatologic toxicities associated with anti-EGFR monoclonal antibody therapy can be managed, minimizing patient discomfort and the need for therapy interruption and/or discontinuation. Additionally, preemptive treatment can reduce dermatologic toxicity severity, ultimately yielding better quality of life.

Keywords: Dermatologic toxicity management; Epidermal growth factor receptor; Patient outcomes; Skin toxicity.

Figure 1

Types of Studies Included in the Systematic Review Abbreviations: CRC = colorectal cancer; EGFR = epidermal growth factor receptor; mAbs = monoclonal antibodies.

Figure 2

Photographs of Skin Rash Occurring During Anti-epidermal Growth Factor Receptor Monoclonal Antibody Treatment According to Body Location and Grade. Grade 1 Skin Rash Is Defined as Papules/Pustules Covering < 10% of the Body. Grade 2 Skin Rash Is Defined as Papules/Pustules Covering 10% to 30% of the Body and Is Associated With Psychosocial Effects and Limiting Daily Life. Grade 3 Rash Is Defined as Papules/Pustules Covering > 30% of the Body That Limit Daily Life and Are Associated With Local Superinfection Requiring Oral Antibiotics

Figure 3

Photographs of (A) Xerosis and (B) Paronchyia Occurring During Anti-Epidermal Growth Factor Receptor (EGFR) Therapy by Grade. The First Symptoms for Xerosis (ie, Rough, Dry Skin) Typically Occur Within 1 to 2 Months of Initiation of anti-EGFR Therapy. Paronchyia (ie, Inflammation of the Nail Folds of the Fingernails and Toenails) Can Lead to Infection and Swelling/Tenderness and Usually Develops After Skin Reactions, Within 20 Days to 6 Months After Treatment Initiation