Durable Intracranial Response to Sacituzumab Tirumotecan in HER2-Negative Salivary Duct Carcinoma With High TROP2...

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.

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.

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.