Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs)

Abstract

Pancreatic neuroendocrine tumours (PanNETs) are rare diseases and a good example of how research is not only feasible, but also of crucial importance in the scenario of rare tumours. Many clinical trials have been performed over the past two decades expanding therapeutic options for patients with advanced PanNETs. Adequate management relies on optimal selection of treatment, which may be challenging for clinicians due to the fact that multiple options of therapy are currently available. A number of therapies already exist, which are supported by data from phase III studies, including somatostatin analogues and targeted therapies (sunitinib and everolimus). In addition, chemotherapy remains an option, with temozolomide and capecitabine being one of the most popular doublets to use. Peptide receptor radionuclide therapy was successfully implemented in patients with well-differentiated gastro-entero-pancreatic neuroendocrine tumours, but with certain questions waiting to be solved for the management of PanNETs. Finally, the role of immunotherapy is still poorly understood. In this review, the data supporting current systemic treatment options for locally advanced or metastatic PanNETs are summarized. Strategies for treatment selection in patients with PanNETs based on patient, disease, or drug characteristics is provided, as well as a summary of current evidence on prognostic and predictive biomarkers. Future perspectives are discussed, focusing on current and forthcoming challenges and unmet needs of patients with these rare tumours.

Molecular Profiling of Well-Differentiated Neuroendocrine Tumours: The Role of ctDNA in Real-World Practice

“…Despite in-depth research on the identification of relevant molecular pathways in NETs [ 16 ], the development of precision medicine approaches represents one of the most relevant challenges in the current management of patients with NENs [ 17 ]. Beyond developments in the arena of nuclear medicine, which is rapidly developing new theragnostic approaches [ 18 ], predictive biomarkers for systemic therapy selection in WdNETs are lacking [ 19 , 20 , 21 ].…”

Simultaneous Resection of Pancreatic Neuroendocrine Tumors with Synchronous Liver Metastases: Safety and Oncological Efficacy

“…While liver resection should be performed in the presence of diffuse, liver involvement also remains to be discussed. Recent advances in interventional radiology procedures including chemo and radioembolization seems to improve local control [1][2][3]. The benefit of liver resection should always to be balanced against the inherent risk of surgery.…”

“…Pancreatic neuroendocrine tumors (PNET) are a rare neoplasm with a biological behavior ranging from indolent to highly aggressive disease. The therapeutic management is based on tumor, disease and patients factors [1,2]. Up to half of all newly diagnosed PNETs present with liver metastases (LM) [3].…”

Observational Study in a Real-World Setting of Targeted Therapy in the Systemic Treatment of Progressive Unresectable or Metastatic Well-Differentiated Pancreatic Neuroendocrine Tumors (pNETs) in France: OPALINE Study

“…Treatment decision for advanced pNET depends on multiple factors including the extent of the disease and tumor characteristics (grade, Ki-67 status, morphology), tumor functionality, tumor biomarkers, tumor burden (large liver tumor load and presence of extrahepatic metastases), individual factors (comorbidities), prior treatment regimens and responses to them including side effects, progression rate and other symptoms [ 18 ]. Ki-67 is considered a crucial element of the decision in the OPALINE study, even if the cut-off of 10% separated the survival curves (data not shown) it was not possible to evaluate it according to the treatment because of low numbers per subgroup.…”