Common Skin Problems With EGFR-TKIs Used for Lung Cancer

Veronica Hackethal, MD

December 22, 2015

The most common skin toxicities associated with epidermal growth-factor receptor tyrosine kinase inhibitors (EGFR-TKIs), which are used in the treatment of non-small-cell lung cancer (NSCLC), are acne-like lesions, itching, dry skin, and nail bed inflammation, according to a Taiwanese study published online on December 9 in JAMA Dermatology.

The study also showed that skin toxicities were similar, for the most part, with three different TKIs: afatinib (Giotrif, Boehringer Ingelheim), gefitinib (Iressa, AstraZeneca), and erlotinib (Tarceva, Genentech/OSI/ Astellas).

"We only found significant differences among incidences of paronychia between first-generation EGFR-TKIs, such as gefitinib and erlotinib, and second-generation EGFR-TKIs, like afatinib," said lead investigator Chia-Yu Chu, MD, PhD, CEO of the International Medical Service Center and associate professor at the National Taiwan University Hospital in Taipei.

After individual variation and cumulative effects were taken into account, the differences remained significant, he added.

Skin toxicities are common adverse effects of EGFR-TKIs, but the incidence varies among clinical trials, Dr Chu explained. The major four skin toxicities of EGFR-TKIs are acneiform eruptions (lesions, usually on the head or chest, that resemble acne), pruritus (itching), xerosis (abnormally dry skin, sometimes with scaling), and paronychia (inflammation at the base of the nail bed). Until now, no direct comparison of these four skin toxicities between the three different TKIs — gefitinib, erlotinib, and afatinib — had been done, the investigators report.

The retrospective study involved patients treated at the National Taiwan University Hospital who received compassionate treatment with afatinib for non-small-cell lung cancer from November 2007 to April 2013. Most patients also received gefitinib or erlotinib before starting afatinib, although some received first-line afatinib. All patients received EGFR-TKI therapy for at least 30 consecutive days, had a minimum 30-day interval between drugs if they received two or more EGFR-TKIs, and had clinical follow-up for at least 6 months.

Specialized dermatologists diagnosed and managed all patients in integrated oncology clinics, likely resulting in more accurate diagnoses than in other clinical trials, Dr Chu pointed out.

The analysis involved 61 patients who received gefitinib, 117 who received erlotinib, and 93 who received afatinib.

Patients most commonly experienced acneiform eruption (67.2% to 76.3%), followed by pruritus, and xerosis (47.5% to 63.4%).

Paronychia was the least common skin toxicity; however, the differences in incidence between gefitinib, erlotinib, and afatinib were significant (9.8% vs 12.8% vs 39.8%; P < .001).

Results were similar for the 21 patients who received sequential gefitinib, erlotinib, and afatinib.

Patients who received EGFR-TKIs for more than 180 consecutive days had earlier onset of paronychia. They also had more dermatologic visits for any skin toxicity in the first 180 days, likely because of increased skin toxicity with afatinib. These visits decreased after the first 6 months, indicating that skin toxicities for different types of EGFR-TKIs can be managed similarly and effectively, the investigators report.

Being on the alert for the four major skin adverse effects of EGFR-TKIs — acne-like lesions on the head and chest, itching, dry skin with scaling, and nail bed inflammation — could aid in the diagnosis and treatment of these conditions, Dr Chu and his colleagues write.

"Early and aggressive dermatologic care is mandatory for patients taking EGFR-TKIs," Dr Chu emphasized.

Dr Chu reports receiving consulting fees, travel support, lectures fees, and/or honoraria from Boehringer Ingelheim, International GmbH, AstraZeneca, and Roche.

JAMA Dermatol. Published online December 9, 2015. Abstract

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