Complete response following trastuzumab-deruxtecan in a man with HER2-overexpressing metastatic, poorly differentiated scrotal carcinoma

Overexpression of human epidermal growth factor receptor 2 (HER2) has been implicated as a molecular driver of numerous solid tumor subtypes. An antibody drug conjugate (ADC) directed to HER2, trastuzumab-deruxtecan, recently gained tumor-agnostic FDA approval for the treatment of advanced HER2-positive (IHC 3+) solid tumors. Here, we present a patient with HER2-positive invasive poorly differentiated scrotal carcinoma treated with trastuzumab-deruxtecan. The treatment resulted in a complete response, with a tolerable side effect profile and ongoing treatment-free survival. Our case adds to the literature suggesting clinical benefit of the use of trastuzumab-deruxtecan in HER2-positive tumors, and underscores the importance of molecular testing for patients with rare tumor subtypes.