Durable Intracranial Response to Sacituzumab Tirumotecan in HER2-Negative Salivary Duct Carcinoma With High TROP2 Expression: A Case Report.

BACKGROUND: Salivary duct carcinoma is an aggressive salivary gland malignancy in which systemic therapy is often guided by androgen receptor and HER2 status. Treatment options are limited for HER2-negative disease after progression on androgen-deprivation therapy and chemotherapy, particularly when active central nervous system (CNS) involvement develops. CASE: A 62-year-old man with androgen receptor-positive, HER2-negative salivary duct carcinoma developed progressive intracranial dural metastases involving the left temporal and occipital regions after surgery, adjuvant radiotherapy, androgen-deprivation therapy, and multiple chemotherapy-based regimens. The dominant lesion was a 33.6-mm left temporal dural-based mass extending across the left tentorial leaflet. Immunohistochemical profiling of archival primary tumor tissue showed high membranous TROP2 expression (H-score, 230). Off-label sacituzumab tirumotecan was initiated at 350 mg every 2 weeks without concurrent corticosteroids or local CNS-directed therapy. Serial magnetic resonance imaging demonstrated sustained regression of the dominant left temporal mass from 33.6 to 15.3 mm (-54.5%), with no new intracranial lesions. Intracranial disease control was maintained for approximately 9 months. Treatment-related Grade 2 oral mucositis and leukopenia improved with supportive care and did not require dose reduction or treatment discontinuation. CONCLUSION: In heavily pretreated, HER2-negative salivary duct carcinoma with high TROP2 expression and progressive intracranial dural metastases, sacituzumab tirumotecan was associated with a durable intracranial response without local CNS-directed therapy. This observation supports further clinical evaluation of TROP2-directed antibody-drug conjugates in salivary duct carcinoma with CNS involvement, while the predictive value of TROP2 expression remains to be established.