Dramatic response to trastuzumab-deruxtecan in metastatic HER2-overexpressing vulvar extramammary Paget's disease: A case report

Background Extramammary Paget's disease (EMPD) is a rare cutaneous in situ adenocarcinoma sometimes associated with invasive malignancy that may evolve to metastatic disease. HER2 alterations have been reported in aggressive cases and may be targetable. Case presentation We report a patient with metastatic vulvar EMPD with HER2 3+ score by immunohistochemistry (IHC) and ERBB2 amplification who progressed after local therapies, surgery, radiotherapy and trastuzumab ± paclitaxel. Off-label trastuzumab-deruxtecan (T-DXd) was started as second-line systemic therapy with marked extracranial and intracranial responses and acceptable toxicity. Conclusion This case supports consideration of HER2-directed antibody-drug conjugates in HER2-positive EMPD when standard options are exhausted.