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

Abstract

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.

A gold mine for drug discovery: Strategies to develop cyclic peptides into therapies

“…Lanreotide autogel and octreotide long‐acting release are two commonly used drugs to treat well‐differentiated NETs, which exhibit preferentially restricted affinity towards SSTR2 . As reported, the hormonal hypersecretion symptoms in about 40% to 60% of the patients with functioning NETs could be effectively controlled by these two long‐acting cyclic peptides . Pasireotide is a multireceptor‐targeted SSA with high affinity towards different SSTR subtypes (SSTR1, 2, 3, and 5), which have been approved for the therapy of Cushing's disease by FDA and EMA …”

The Evolution of Neuroendocrine Tumor Treatment Reflected by ENETS Guidelines

“…Besides SSAs, ENETS separately published instructions for safe use of systemic therapy. [61]. Future interests lie in optimal dosing of SSAs, new forms of SSAs (single versus multiple SSA receptor), new formulations and whether to continue SSAs during second-line therapy, like PRRT using radiolabeled SSAs and targeted therapy.…”

“…For example, for the patient with hypertension everolimus could be more suitable and vice versa for the patient with diabetes. The characteristics and treatment of side effects have been described in the standard of care for systemic therapy [61]. An important role for ENETS will continue to be the judging of the available evidence for drugs to advise the clinician through its guidelines on selecting the most appropriate drug for the patient.…”

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors

“…The following 9 papers [3,4,5,6,7,8,9,10,11] are the result of an Advisory Board Consensus Conference meeting. These ENETS guidelines for the standards of care in NET provide a tool to accurately assess the diagnosis of NET and provide practical recommendations for the use of surgery, and the different systemic therapeutic options that are available for the management of NET.…”