New and emerging systemic therapy options for well-differentiated gastroenteropancreatic neuroendocrine tumors

ABSTRACT

Introduction: Well-differentiated gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with a wide range of clinical behavior. Multiple treatment modalities exist, including novel and emerging systemic options, and an understanding of the advantages and disadvantages of each is imperative for optimizing the outcomes of patients with GEP-NETs.

Areas covered: While surgical resection remains the preferred treatment for localized well-differentiated GEP-NETs, treatment of unresectable disease depends on its extent, location, and distribution as well as underlying aspects of tumor biology. Isolated hepatic metastases can be successfully treated with liver-directed therapies such as hepatic arterial based therapies or ablation. Diffuse metastatic disease often requires systemic treatments such as molecular-targeted therapeutics, peptide receptor radionuclide therapy (PRRT), or traditional chemotherapy. Somatostatin analogs are often the primary treatment option capable of simultaneously inhibiting hormone production and slowing tumor growth.

Expert opinion: Recent advances in systemic treatment options for advanced well-differentiated GEP-NETs have emerged due to an improved understanding of the molecular mechanisms responsible for tumor development and progression. Future research is needed to determine the optimal indications for and sequencing of these novel therapies.

KEYWORDS:

• Carcinoid
• NET
• peptide receptor radionuclide therapy
• PRRT
• somatostatin

Article Highlights

• GEP-NETs are clinically heterogeneous.

• Surgical resection, when possible, remains the primary option for localized tumors.

• Non-surgical candidates can be treated in certain cases with liver-directed therapies such as TACE, TARE, or TAE.

• Targeted therapies such as mTOR and tyrosine kinase inhibitors, PRRT, and somatostatin analogs are important treatment modalities for patients with advanced disease.

• New data is emerging regarding novel molecular and genetic tools to help predict the response of tumors to molecular inhibitors and other treatment modalities.

• Chemotherapy remains a mainstay of treatment in cases of advanced disease and efforts to individualize therapy are currently underway.

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

One referee declares having received research Funding from IPSEN Pharma and Novartis as well as salaries for Talks from Novartis and IPSEN Pharma. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

The project was supported by a grant from the National Center for Advancing Translational Sciences.