Abstract
SummarySalivary 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.
Highlights
Preliminary data of a phase II basket trial presented at ASCO 2019 reported overall response rates (ORR) upon TDM-1 of up to 90% in salivary ductal carcinoma (SDC) previously treated with trastuzumab (NCT02675829)
Chemotherapy showed minor efficacy and the evaluation of therapy success is limited by the small number of patients
Targeted therapies are on the rise and potential molecular targets such as human epidermal growth factor receptor 2 (HER2), neurotrophic tyrosine receptor kinase (NTRK) and androgen receptor (AR) do exist
Summary
Received: 21 February 2020 / Accepted: 23 April 2020 / Published online: 13 May 2020. Active agents that were tested mainly in phase II studies include cisplatin [10, 11], mitoxantron [12, 13], epirubicin [14] and vinorelbine [15] It has to be kept in mind that disease stabilization was far more common in all this studies than an objective response, which might be due to the slowly progressing nature of this disease [9]. Combination therapy with cisplatin, doxorubicin and cyclophosphamide (CAP) provided overall response rates (ORR) between 18–33% in a total of 4 studies [16,17,18,19]. No responses have yet been reported in previously treated ACC patients [2]
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