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Cutaneous complications of molecularly targeted therapy and other biologic agents used for cancer therapy

Authors
Aimee S Payne, MD, PhD
Diane MF Savarese, MD
Section Editors
Reed E Drews, MD
Maja Mockenhaupt, MD, PhD
Deputy Editor
Rosamaria Corona, MD, DSc

INTRODUCTION

Over the last two decades, novel antineoplastic therapy strategies have evolved that exploit some of the molecular abnormalities that have been detected in certain types of cancer. While the targets of these agents differ, collectively they are referred to as molecularly targeted agents. Many of these agents, particularly those interfering with signal transduction (eg, epidermal growth factor receptor [EGFR] inhibitors, multitargeted small molecule tyrosine kinase inhibitors), are associated with prominent and sometimes dose-limiting dermatologic complications [1].

This topic review will cover dermatologic toxicities seen with several classes of biologic and molecularly-targeted agents, including drugs and monoclonal antibodies targeting the EGFR, other therapeutic monoclonal antibodies, small molecule tyrosine kinase inhibitors, and biologically active cytokines. Cutaneous reaction patterns seen with conventional cytotoxic agents and checkpoint inhibitor immunotherapies used for advanced melanoma and non-small cell lung cancer (ipilimumab, pembrolizumab, nivolumab) are discussed elsewhere. (See "Cutaneous complications of conventional chemotherapy agents" and "Toxicities associated with checkpoint inhibitor immunotherapy", section on 'Rash and mucosal irritation'.)

EGFR INHIBITORS

The array of drugs that inhibit the epidermal growth factor receptor (EGFR) include three therapeutic monoclonal antibodies (cetuximab, panitumumab, necitumumab) and five orally active small molecule EGFR inhibitors (gefitinib, erlotinib, lapatinib, afatinib, and osimertinib). As a group, these drugs have prominent dermatologic side effects, the most common of which is a papulopustular acneiform eruption (table 1). (See "Systemic chemotherapy for metastatic colorectal cancer: Completed clinical trials" and "Systemic therapy for advanced non-small cell lung cancer with an activating mutation in the epidermal growth factor receptor", section on 'EGFR TKI toxicity' and "Systemic treatment for HER2-positive metastatic breast cancer".)

Acneiform eruption — The most common cutaneous reaction pattern with the EGFR inhibitors is a diffuse papulopustular acneiform eruption, which is noted in more than two-thirds of patients receiving any of these agents (although severe in only 5 to 10 percent) [2-5]. The eruption consists of erythematous follicle-based papules and pustules, typically without comedones.

The acneiform eruption is often dose-dependent, and typically begins early, within one week of treatment initiation (picture 1) [6,7]. The lesions typically occur on the face, trunk, and extremities, sparing the palms and soles. Scaling of the interfollicular skin may also be present. Significant pruritus accompanies the cutaneous eruption in up to one-third of patients [8].

                          

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