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Advanced Pancreatic Neuroendocrine Neoplasms: Which Systemic Treatment Should I Start With?

  • Neuroendocrine Neoplasms (NS Reed, Section Editor)
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Abstract

Purpose of Review

Pancreatic neuroendocrine neoplasms (panNENs) often present as advanced disease and there is little data to guide treatment sequencing in the advance disease setting. Therefore, we aim to provide a comprehensive summary of the current evidence supporting the use of systemic treatment for patients with diagnosis of advanced and metastatic panNENs, as well as to provide strategies for treatment selection and address challenges for treatment selection and sequencing of therapy.

Recent Findings

Substantial advances have been made and many clinical trials have been performed over the past two decades expanding therapeutic options available for patients with advanced panNETs. Available systemic treatments for patients with well-differentiated pancreatic neuroendocrine tumors include somatostatin receptors ligands (SRLs), traditional cytotoxic chemotherapy regimens, peptide receptor radiotherapy (PRRT), and biologically targeted therapies, whereas patients with poorly differentiated neurodocrine carcinomas have more limited treatment options. Despite these advances, no clear guidelines exist to support the best sequence of treatments, not only the first-line, but also subsequent lines of therapy in patients with panNENs. Advances in molecular research and discovery of biomarkers for response allowing a more personalized approach to the multimodality therapy of panNENs are still limited. Understanding the impact of previous therapies on subsequent treatment efficacy and toxicity is also an ongoing research question.

Summary

In the absence of definite predictive markers and paucity of comparative randomized trials, along with the heterogeneity of this patient population, systemic therapy selection in advanced non-resectable disease should be patient centered and often require evaluation within a multidisciplinary setting. The specific clinical context of the patient, with assessment of individual patient clinical and pathological features, somatostatin receptors imaging, and goals of treatment must all be considered when deciding on systemic therapy in the patient. Additional research is needed to address the gap in knowledge regarding optimal sequencing and timing of therapies and to provide individual care.

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Authors and Affiliations

  1. Department of Medical Oncology and Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    Victor Rodriguez-Freixinos & Simron Singh

  2. Department of Pharmacy, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada

    Alia Thawer

  3. Department of Medical Oncology, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VIHO), Barcelona, Spain

    Jaume Capdevila

  4. Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Diego Ferone

  5. Endocrinology, Department of Internal Medicine and Medical Specialties (DIMI) and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy

    Diego Ferone

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  1. Victor Rodriguez-Freixinos
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Correspondence to Simron Singh.

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Victor Rodriguez-Freixinos and Diego Ferone declare no conflict of interest. Alia Thawer has received research funding from Novartis (Melanoma Guideline) and AstraZeneca (local quality improvement work); has received speaker’s honoraria from Novartis (NET allied health education and melanoma education) and Pfizer (breast allied health education); and has received compensation from AbbVie for service as a consultant. Jaume Capdevila has received research funding from Novartis, Pfizer, Bayer, Eisai, Advanced Accelerator Applications, and AstraZeneca; and has received compensation from Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Eli Lilly, Sanofi, and Merck Serono for service as a consultant. Simron Singh has received research funding/fellowship support from Pfizer, and has received compensation from Ipsen and Novartis for service as a consultant.

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This article is part of the Topical Collection on Neuroendocrine Neoplasms

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Rodriguez-Freixinos, V., Thawer, A., Capdevila, J. et al. Advanced Pancreatic Neuroendocrine Neoplasms: Which Systemic Treatment Should I Start With?. Curr Oncol Rep 23, 80 (2021). https://doi.org/10.1007/s11912-021-01071-5

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