An Overview on the Sequential Treatment of Pancreatic Neuroendocrine Tumors (pNETs)

Abstract

Patients suffering from pancreatic neuroendocrine tumors (pNETs) are now candidates to receive novel approved drugs that have demonstrated benefit in disease control rate and delay the time taken for tumor progression in Phase III clinical trials; for example, sunitinib, everolimus and lanreotide. Though pNETs represent a rare and heterogeneous disease, recent approaches are being taken to better understand the molecular pathways involved in carcinogenesis. Consequently, new treatment strategies are now available and others still under investigation show promising results. However, some questions around how to approach patients with pNETs are still unresolved, such as what the best sequence of treatments we can offer to each of our patients in the clinic at any time of their disease would be. Therapeutic decisions are, at the moment, guided by clinical judgment, based on different parameters coming from retrospective analysis and non-randomized clinical trials. However, advances in genomic research would lead to a more precise approach using therapeutic targets that would also allow the development of new agents, prognostic or predictive biomarkers and a better understanding of resistance mechanisms. The following article is a comprehensive review of the approved and investigational drugs in pNET, and highlights the current concerns about treatment sequencing, but also provides an update of some of the present and future efforts for an improvement in the therapeutic algorithm of the disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s40487-015-0007-6) contains supplementary material, which is available to authorized users.

Management Options for Advanced Low or Intermediate Grade Gastroenteropancreatic Neuroendocrine Tumors: Review of Recent Literature

“…The management of patients with metastatic NETs has been revolutionized by the development of new systemic and biological treatment strategies such as molecular targeted therapies with everolimus and sunitinib, PRRT, as well as revealing the antiproliferative properties of SA. The growing list of effective therapeutics with favorable toxicity profiles has given rise to novel multidisciplinary approaches in the management of patients with advanced NETs including the emerging concept of sequential treatment [ 118 ]. Growing body of evidence from randomized clinical trials comparing the effects of different therapeutic modalities makes it unclear when to apply a given option, what combination therapeutic approach should be used and in what sequence, how long treatment should be continued, and in what subgroup of patients a particular treatment option should be used.…”

Diabetes and pancreatic neuroendocrine tumours: Which interplays, if any?

“…For their part, SSAs remain the recommended first-line treatment for most somatostatin-receptor-expressing G1/G2 PanNETs, whether functioning or not. Further treatment decision should be based on tumour characteristics, tumour related symptoms, comorbidities, and the local availability of various alternatives, but the ideal sequence of drugs after (or together with) SSAs is still a matter of debate [1].…”

Targeting Angiogenesis in Pancreatic Neuroendocrine Tumors: Resistance Mechanisms

“…Glucagonoma is associated to necrolytic migratory erythema, diabetes, and diarrhea. The clinical syndrome of VIPoma is watery diarrhea with hypokalaemia and hypochlorhydria [4].…”

“…In terms of survival, patients with metastatic P-NETs disease present a median overall survival (OS) of about 3.6 years [2] and 5-year survival rate of 30.2%. Nowadays, 65% of P-NETs are diagnosed as unresectable or metastatic disease, with a consequent worse prognosis [3,4,5].…”