Systemic therapy for metastatic salivary gland tumors-challenges and novel concepts

Salivary gland cancers (SGC) are a rare and heterogeneous group of malignancies. Most frequently tumors arise in the parotid gland. The most common histologic subtypes are adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC). Rare subtypes include salivary ductal carcinoma (SDC), mammary analogue secretory carcinoma (MASC) and adenocarcinoma not other specified (AC NOS). For locally advanced or metastatic disease, chemotherapy has been the mainstay of therapy. The course of disease differs markedly between the subtypes, especially ACC usually presents as slowly progressing disease. Due to the rarity of these tumors only small phase I/II studies exist, which report efficacy of cytotoxic regimens in advanced SGC. However, due to advances in the understanding of tumor biology and molecular testing, drugable genetic changes like androgen receptor (AR) status, HER2/neu overexpression and neurotrophic tyrosine receptor kinase (NTRK) gene fusion have evolved as potential therapy targets in subsets of SGC. Consequently therapy with androgen receptor blockade (ARB) can be offered to patients with AR expressing tumors. Anti-HER2 therapy with trastzumab is an option for the treatment of tumors with overexpression of HER2/neu and finally NTRAK inhibitors can be used for tumors harboring a NTRK gene fusion. Taken together, due to the small number of patients, data from large phase III studies for the treatment of SGC are missing. However, promising targeted therapy approaches have been recently undertaken.