Severe Dermatologic Toxicity During Amivantamab-Lazertinib Treatment in Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer.

Amivantamab is an epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) antibody. Lazertinib is an EGFR tyrosine kinase inhibitor with central nervous system penetration. Used in combination, this targeted therapy is effective in treating non-small cell lung cancer (NSCLC). However, it has been associated with severe dermatologic adverse reactions. A 61-year-old woman with a history of EGFR-mutated NSCLC with brain metastases on amivantamab-lazertinib therapy presented for follow-up with drainage from her scalp incision after undergoing a right parietal craniotomy and mass excision five months prior. The patient denied constitutional and neurologic symptoms, but reported yellow staining on her pillow. Examination initially demonstrated yellow fibrinous exudate and hair matting along the surgical incision. Computed tomography (CT) of the head revealed overlying scalp swelling and minimal extra-axial dural thickening over the prior right parietal craniotomy site with stable intracranial metastatic lesions. Due to concern for dehiscence, her biologic therapy was paused, and she was taken to the operating suite where no evidence of infection, delayed healing, or wound dehiscence was noted. A 10 × 5 cm area of patchy granulation tissue and ulceration was observed along the right parietal scalp. Biopsy revealed granulation tissue and multinucleated giant cells and was negative for tumor. Given the risk of malignant progression with all targeted therapy paused, the patient was restarted on amivantamab monotherapy. Following disease progression two months later, she was transitioned to carboplatin and etoposide. EGFR is widely expressed in skin keratinocytes and intimately involved in epithelial differentiation. Therapies targeting EGFR, such as amivantamab plus lazertinib, are associated with adverse dermatologic reactions, ranging from dry skin to severe scalp ulceration, which can interrupt treatment, contribute to poorer clinical outcomes, and reduce quality of life. Standard of care includes limiting sun exposure and avoiding alcohol-based topical agents. The use of daily prophylactic antibiotics, such as oral doxycycline, topical clindamycin, chlorhexidine wash, and ceramide moisturizer, may significantly reduce the risk of adverse skin reactions. Implementation of this multicomponent regimen reduced the rate of severe scalp reactions from 26% to 10% relative to the standard of care, with sustained benefit observed for at least six months.