Precision-directed therapy in salivary duct carcinoma

Salivary ductal carcinoma is a rare, aggressive salivary gland carcinoma with poor prognosis and high relapse rate. In recurrent metastatic cases, the median survival is only 5 months. Despite the treatment with multimodal therapeutic strategies, conventional treatments demonstrate a limited effect on long-term survival of the patients. In this study we report two cases of salivary ductal carcinoma patients managed with precision-directed, biomarker-guided therapeutic approaches. In the first case androgen receptor (AR) and HER2 positivity by immunohistochemistry analysis were detected. The patient was treated with AR directed targeted therapy enzalutamide and Leuprolide as maintenance therapy. Disease progression with an emergent HER2 expression by immunohistochemistry led to the inclusion of trastuzumab and pertuzumab. While in the second case the patient progressed on neoadjuvant chemotherapy and the subsequent molecular analysis revealed high expression of PD-L1 and was treated with pembrolizumab in combination with chemotherapy. Follow up assessment revealed treatment durable responses and disease control in both the patients. These cases underscore the potential role of comprehensive molecular profiling-guided personalised therapeutic approaches in the management of advanced SDC patients. • Salivary ductal carcinomas show potential druggable molecular alterations and has promising efficacy • AR, ERBB2, HRAS, NF1, TP53, PIK3CA, MYC, loss of PTEN and CDKN2A are the most frequently seen molecular alterations