Skin Reactions and Other Underappreciated Dermatologic Side Effects of Cancer Therapies

Abstract

Cutaneous adverse events (cAEs) are among the most common toxicities associated with modern cancer therapies, which are particularly heightened among immunotherapies and targeted agents. Despite being frequently immune-mediated, the majority of cAEs are mild to moderate and can be effectively managed without interruption of anticancer treatment. In immunotherapies-receiving patients, common phenotypes of cAEs include eczema-like, lichenoid, psoriasiform, vitiligo-like, and bullous eruptions. Targeted therapies including epidermal growth factor receptor inhibitors, BRAF inhibitors/MEK inhibitors, and phosphoinositide 3-kinase inhibitors are frequently associated with papulopustular eruptions, xerosis, paronychia, and photosensitivity. Mechanistically, cAEs may result from on-target immune activation, which correlates with treatment efficacy, or off-target hypersensitivity. Notably, certain phenotypes such as vitiligo, alopecia areata, and lichenoid reactions have been associated with improved survival in melanoma and non-small cell lung cancer. Management is guided based on the Common Terminology Criteria for Adverse Events grading, emphasizing the role of topical therapies for mild cases, systemic corticosteroids or immunosuppressants for moderate-to-severe reactions, and biologic or novel topical agents for steroid-refractory disease. By timely and appropriate intervention, most cAEs are manageable and may carry favorable prognostic significance. Early dermatologic collaboration is essential to reduce morbidity and ensure uninterrupted oncologic therapy.

Keywords: Biologic therapies; Cancer therapies; Cutaneous adverse events; Immune checkpoint inhibitors; Targeted therapies.