Systemic Therapy in Salivary Gland Carcinoma

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 pathogenesis, and it can reflect diverse clinical behaviors. According to the World Health Organization (WHO) classification (2017), more than 20 malignant histotypes are currently identified, but for clinical purposes we can split SGCs in two big groups: adenoid cystic carcinoma (ACC) that is the most common histotype in metastatic patients (60%) and other histotypes (here defined as non-ACC). This latter group includes several histotypes rarer than ACC, such as mucoepidermoid carcinoma, salivary duct carcinoma (SDC), adenocarcinoma, not otherwise specified (NOS), myoepithelial carcinoma, etc. ACC population is typically characterized by a slow-growing and indolent evolution, while non-ACCs are more aggressive histotypes. This could explain a different clinical management of ACC in respect to non-ACC. In fact, bearing in mind that a standardized first-line treatment for advanced SGCs is far to be defined, only in ACC population a watchful waiting approach may be also considered in the absence of symptomatic and/or rapidly progressive disease. Having said that, if the start of systemic therapy is indicated, chemotherapy (cisplatin alone or in combination with other chemo agents) is the most recommended treatment, both in ACC and non-ACC groups. To date, androgen deprivation therapy (ADT) is the only effective tailored approach active in AR-expressing SDC and adenocarcinoma, NOS, and an ongoing international trial (NCT01969578) will clarify the role of ADT as frontline treatment over chemotherapy. Other targeted agents have not demonstrated till now any advantage in patients with metastatic SGCs. However, comprehensive better understanding of biology and genetics of these rare cancers could lead to identifying further druggable targets and potentially improving patient’s outcome. Notably, data on immunotherapy in SGCs are still scarce, but the ongoing studies could contribute to assess its role in these patients.