Systemic and Targeted Therapies in Adenoid Cystic Carcinoma

Adenoid cystic carcinoma (ACC) is an often-indolent type of salivary gland cancer (SGC). A subset of patients develops progression or aggressive disease warranting systemic therapy in the recurrent/metastatic (R/M) setting. We recommend genomic testing for all patients with R/M disease to aid with prognostication and eligibility for potential experimental therapies. Here, we review the currently available treatment options (cytotoxic chemotherapies and vascular endothelial growth factor receptor (VEGFR)-targeting tyrosine kinase inhibitors (TKIs)). Based on limited data, we nominate regimens which may have more favorable efficacy profiles. Among the cytotoxic chemotherapies, several regimens are acceptable when incorporating a platinum agent. Among the VEGFR-targeting TKIs, lenvatinib and axitinib are the preferred options. Larger, randomized studies prioritizing combinations with mechanistic synergism are needed. Predictive biomarkers are critical, as there is currently little evidence to guide sequencing of available options for individual patients. Immunotherapy is an available option, but has been associated with only modest benefit in ACC. We go on to review other therapies that have been studied and nominate those with promise based on early clinical data.