Incidence of Adverse Cutaneous Reactions to Epidermal Growth Factor Receptor Inhibitors in Patients with Non-Small-Cell Lung Cancer

Abstract

<b><i>Background:</i></b> Epidermal growth factor receptor (EGFR) inhibitors are routinely used in advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, their use is associated with gastrointestinal and cutaneous toxicities, including acneiform eruptions, pruritus, xerosis, nail and hair changes. Aside from reducing patients’ quality of life, such cutaneous reactions have a considerable impact on the oncologic treatment given that dose reduction or even drug discontinuation may be necessary, especially for the severe forms. <b><i>Objectives:</i></b> To assess the incidence, impact on treatment and management of EGFR inhibitor-related cutaneous reactions in patients with NSCLC. <b><i>Methods:</i></b> We conducted a prospective observational study on 87 consecutive patients with advanced NSCLC treated with EGFR-tyrosine kinase inhibitors from January to December 2019. Patients who developed mucocutaneous reactions were evaluated and treated by both oncologists and dermatologists, and underwent dermatologic follow-up until resolution of the cutaneous reaction. Demographic and clinical data were collected for each patient, and the severity of the cutaneous reaction was graded using the Common Terminology Criteria for Adverse Events. <b><i>Results:</i></b> Seventy-one patients (81.6%) developed cutaneous reactions. The number of cutaneous reactions per patient was 1 in 37%, 2 in 41% and 3 or more in 22%. The most common cutaneous reactions included acneiform eruptions (56.3%), xerosis ± asteatotic eczema (48.3%), nail changes (39.1%), mucositis (29.9%), pruritus (24.1%) and hair changes (12.6%). Afatinib was associated with a higher rate of nail changes and mucositis (<i>p</i> < 0.01 and <i>p</i> < 0.005, respectively) compared to other agents, while no patient-related predictive factors were identified. Dose reduction was performed in 18% of patients. Multidisciplinary management involving dermatologists allowed to resume the drug in all patients who had discontinued it due to the cutaneous reactions. <b><i>Conclusions:</i></b> A multidisciplinary approach to EGFR inhibitor-related cutaneous reactions is advantageous and can reduce the need to discontinue oncologic treatment.

The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies

“…Likewise, all‐grade OMT was noted to occur in 2% to 50% of patients who received lapatinib, an HER2 inhibitor, with an RR of 1.67 (95% CI, 1.02‐2.3; P < .04) 72 . The small‐molecule EGFR inhibitors that have been reported in association with mucositis are erlotinib, afatinib, and gefitinib 73 …”

Acneiform eruption induced by molecularly targeted agents in antineoplastic therapy: A review

“…Rash severity is classified into grades that depend on the affected area, severity, and superinfection (Table 3). Acneiform eruption in most patients is generally classified as grade 1-2, 29,30 which is mild and usually manageable but can cause significant discomfort. Moderate or severe toxicities can sometimes occur, which always leads to dose modification or interruption.…”

“…Oral isotretinoin (0.3-0.5 mg/kg) or prednisone (0.5 mg/ kg) may be used to control the skin reactions. 29 Grade 4 reactions are extremely rare, and patients with skin reactions of this grade should be treated in specialized burn care units.…”

Mechanism of Lethal Skin Toxicities Induced by Epidermal Growth Factor Receptor Inhibitors and Related Treatment Strategies

“…Patients with periungual granulomas can be treated with nitrate first. If there is no response, then curettage and cauterization can be utilized ( 133 , 148 , 161 ). Therapeutic measures are shown in more detail in Table 5 .…”

“…2 Continue EGFR inhibitors at original dose; silver nitrate solution 20% weekly (administer cryotherapy or other chemical/electric cauterization if granulation); povidone-iodine 2% ointment; topical betamethasone valerate 0.1% ointment (2-3 times, qd); oral antibiotics are recommended; reassess after 2 weeks (133, 136, 142, 149) 3Temporary discontinuation of EGFR inhibitors; topical clobetasol cream (2-3 times, qd); povidone-iodine 2% ointment; systemic antibiotics oral or intravenously following pathogenic culture; continue to apply topical antibiotics; reassess after 2 weeks(136,142,148,149,161) …”