ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Systemic Therapy - Biotherapy and Novel Targeted Agents

Systemic therapies established in the management of patients with neuroendocrine tumors (NETs) include somatostatin analogs and interferon-α, also referred to as biotherapy. Recent randomized controlled studies have extended the knowledge on the frequency of side effects associated with biotherapy. More recently, novel targeted drugs, such as the mammalian target of rapamycin inhibitor everolimus and the multiple tyrosine kinase inhibitor sunitinib, have been introduced in the management of NETs. Although targeted drugs are generally well tolerated, with most adverse events being of mild to moderate severity and manageable, novel targeted drugs exhibit a distinct adverse event profile that warrants guidance for appropriate diagnostic and therapeutic management. This is particularly important given the widespread and potentially long-term use of everolimus in a broad spectrum of NETs and of sunitinib in pancreatic NETs. This review will focus on the most relevant toxicities associated with biotherapy and novel targeted drugs and on their management. For each drug class indication, administration and dosing schedule, most frequent adverse events, actions and dose adjustments for adverse events as well as their monitoring are presented. This review further covers the evaluation of treatment effect, patient information, drug interactions, and information on pregnancy.