New Data on Systemic Therapy of Salivary Gland Tumors

Abstract

Malignant salivary gland cancers (SGCs) are a very heterogeneous group of tumors including several disease entities that are often completely different from each other. One of the most important divergences is the histopathological picture. This may be the mirror of a different genetic basis and can translate in a particular clinical behavior. According to the World Health Organization (WHO) classification (2017), more than twenty malignant histotypes are currently identified but, in brief, we can separate all SGCs in two big groups: adenoid cystic carcinoma (ACC), that is the most common type (60%), and non-ACC. The latter includes many other histotypes rarer than ACC, such as mucoepidermoid carcinoma, salivary duct carcinoma, adenocarcinoma, not otherwise specified, epithelial-myoepithelial carcinoma, etc. The ACC population is typically characterized by a slow-growing and indolent evolution whilst non-ACCs contain more aggressive histotypes, albeit that also in this group some histotypes may behave more indolent than others. The different behavior of these two groups to a large extent explains the different clinical management of ACC versus non-ACC. There is no standardized first line treatment for advanced SGCs. Moreover, it is of importance to note that in the ACC population a watchful waiting approach may be considered in the absence of symptomatic and/or rapidly progressive disease. Once systemic therapy is indicated, chemotherapy (cisplatin alone or in combination with other chemotherapeutic agents) is the most recommended treatment, both in the ACC group and the non-ACC group. To date, there is only one other effective treatment option of systemic therapy in SGCs: androgen deprivation therapy (ADT) in androgen receptor (AR) positive SGCs, which represent the best opportunity as second-line therapy in this specific subgroup. An ongoing international trial (NCT01969578) will clarify the role of ADT as front-line over chemotherapy in AR+ SGCs. Considering the other targeted therapies, all of them failed to show any advantage in this setting even if a comprehensive better understanding of biology and genetics of SGCs could lead to identify further druggable targets and help to find more active treatments. Notably, data on the use of immunotherapy in SGCs are still scarse but results of ongoing studies are eagerly awaited.