Approaches to the Management of Metastatic Adenoid Cystic Carcinoma

SIMPLE SUMMARY: Patients with adenoid cystic carcinoma (ACC) often experience late distant metastasis years after definitive therapy, most commonly to the lungs. Currently, there is little consensus on the optimal treatment regimens for metastatic ACC, which typically confer modest clinical benefit. Here, we outline management approaches for metastatic ACC in the context of pertinent ACC biology. We summarize the most commonly utilized systemic treatment regimens, review methods of local control for oligometastatic lung disease, and highlight emerging molecular targets with promise for advancing ACC management in the future. ABSTRACT: High rates of recurrence and distant metastasis are a foremost challenge in the management of adenoid cystic carcinoma (ACC), occurring in approximately 40% of all ACC patients. Despite the morbidity and mortality resulting from recurrent/metastatic (R/M) disease, there are no FDA-approved systemic agents for these patients. In this review, we summarize pertinent ACC pathophysiology and its implications for different systemic treatment regimens in R/M ACC. We review the evidence for the most widely used systemic agents — cytotoxic chemotherapy and tyrosine kinase inhibitors (TKIs) targeting VEGFR — in addition to immune checkpoint inhibitors and non-TKI biologic agents. Exciting emerging targets for R/M ACC, including inhibitors of Notch signaling, stemness, PRMT5, and Axl, are also discussed. Lastly, we review local therapies for small-volume lung disease in patients with oligometastatic ACC, specifically pulmonary metastasectomy and stereotactic body radiation therapy (SBRT). Future development of targeted molecular agents which exploit the underlying biology of this disease may yield novel therapeutic options to improve clinical outcomes in patients with R/M ACC.