Biomarker‐Driven Initial Systemic Therapy Enabling Curative‐Intent Treatment in Non‐Metastatic Unresectable Salivary Duct Carcinoma: A Multi‐Institutional Retrospective Study

Background Optimal treatment for non‐metastatic unresectable salivary duct carcinoma (SDC) remains unclear. We compared outcomes of upfront biomarker‐targeted systemic therapy and radiotherapy. Methods We retrospectively analyzed the Joint SDC Study Group registry. Thirty‐one patients with centrally confirmed non‐metastatic unresectable SDC were classified by initial treatment (radiotherapy or systemic therapy). Systemic therapy included trastuzumab plus docetaxel, combined androgen blockade, or chemotherapy. Progression‐free survival (PFS) and overall survival (OS) were analyzed. Results Systemic therapy showed better PFS than radiotherapy (3‐year PFS 47.6% vs. 30.0%, p = 0.031) without OS difference. Trastuzumab plus docetaxel showed the highest response rate (75%) and enabled curative‐intent treatment in all cases, with the best PFS (3‐year 87.5%, p = 0.012). Conclusions Given the retrospective design and limited sample size, these findings should be regarded as hypothesis‐generating. An upfront trastuzumab‐based therapy followed by curative‐intent treatment may be a promising option for selected patients with HER2‐positive unresectable SDC.