Severe, Atypical Skin Reactions With Amivantamab in NSCLC

A case series of epidermal growth factor receptor (EGFR) exon 20 insertion–mutated advanced non–small cell lung cancer patients with dermatologic adverse events (dAEs) subsequent to treatment with amivantamab showed classic toxic effects associated with EGFR inhibitors and atypical presentations. Toxic effects, however, were mitigated by dose interruptions, dAE management, and amivantamab dose reductions, allowing for cancer therapy continuation in all cases. Amivantamab doses were reduced in 5 out of 6 cases, according to a research letter published in JAMA Dermatology.

The EGFR exon 20 insertion–mutation portends insensitivity to EGFR tyrosine kinase inhibitors and poor prognosis. Amivantamab, a bispecific monoclonal antibody targeting EGFR and mesenchymal epithelial transition factor (MET) is Food and Drug Administration approved for this population. Acneiform eruptions and pruritus are the most common dAEs associated with EGFR inhibitors, with xerosis, fissures, and nail and hair changes occurring additionally. While no FDA-approved monoclonal antibody targets MET exclusively, capmatinib and tepotinib (both tyrosine kinase inhibitors) inhibit MET. They have been associated with photosensitivity, acneiform rash, paronychia, xerosis, pruritus, and mucositis.

The Belzer et al. letter reviewed six consecutive cases (mean age, 58) of dAEs associated with amivantamab at two academic health centers (treated June 2021 to August 2022) in order to describe dAEs associated with amivantamab use. “I suspect the rate of dAEs with amivantamab is similar to the rate of dAEs associated with first- and second-generation EGFR inhibitors, where the majority of patients, actually 75%-90%, develop cutaneous toxicity,” said Jonathan Leventhal, MD, Yale University, New Haven, Conn., corresponding author for the Belzer et al. letter.

Time from treatment initiation with amivantamab to dAE ranged from less than 1 month to 4 months. All dAEs were grade 2 or 3 and all included acneiform eruptions. These were widespread in four cases and in another case complicated by impetiginization (culture results positive for methicillin-susceptible Staphylococcus aureus), and a further case was limited to the scalp, face, upper back, and upper chest. Others with widespread acneiform eruption included the face with hyperkeratotic crust of the scalp and dermatitis of the posterior neck. Fissuring of the palms and soles was noted in two cases with widespread acneiform eruptions. Paronychia with pyogenic granulomas was reported in four cases. Another case included onycholysis with suppurative paronychia.

In five cases amivantamab was stopped but successfully reinitiated at 67%-75% of the original dose. In one case amivantamab was continued at the original dose.

Doxycycline at 100 mg twice daily was included among all of the treatments for cutaneous dAEs. Silver nitrate cautery was applied for pyogenic granulomas in clinic. The case of grade 3 acneiform eruption of the scalp and face was treated with hydrogen peroxide soaks with debridement in clinic, doxycycline, aluminum acetate soaks, and triamcinolone ointment. All dermatologic cases resolved fully without scarring.

“It is very likely that this series highlights the more severe and unusual presentations of dAEs which were referred to oncodermatology. I suspect milder presentations were likely managed by oncologists,” Dr. Leventhal said in the interview.

“It is important for dermatologists and oncologists to be aware of the more severe and atypical dAEs associated with this novel FDA-approved targeted therapy.” Dr. Belzer said. “As amivantamab use increases, oncologists and dermatologists need to collaborate to ensure swift diagnosis and management of dAEs.”

One trial, the authors stated, revealed more than half of patients receiving EGFR inhibitors taking preemptive treatment with moisturizers, sunscreen, topical corticosteroids, and an oral tetracycline to have more than a 50% reduction in grade 2 or higher dAEs. Belzer et al. concluded that prophylactic treatment, including sun protection, should be considered before initiating treatment with amivantamab.

A limitation of the study, Belzer et al. acknowledged, was the small sample size.

Dr. Leventhal reported receiving personal fees from the advisory boards of Sanofi, Regeneron, and La Roche-Posay as well as clinical trial funding from Azitra and OnQuality Pharmaceuticals outside the submitted work.

This article originally appeared on, part of the Medscape Professional Network.

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