Therapeutic strategies for patients with neuroendocrine neoplasms: current perspectives

ABSTRACT

Introduction

Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies mainly arising in the gastroenteropancreatic (GEP) and bronchopulmonary systems, with steadily increasing incidence. The therapeutic landscape has widened and the therapeutic strategy should be based on new sequences and combinations, still debated.

Areas covered

Herein, we provide an overview of current approved pharmacological treatments in patients with NENs, with the aim to summarize evidence of efficacy of the main different options in GEP and pulmonary NENs, principally focusing on somatostatin analogs (SSAs), targeted therapy with everolimus and sunitinib, peptide receptor radionuclide therapy (PRRT) and chemotherapy. We discuss biological rationale and toxicities, including current indications according to differentiation and placement in the therapeutic algorithm, clinical trials, and combinations. Furthermore, we recommend areas for further research.

Expert opinion

Therapeutic management of patients with NENs represents a challenge for clinicians and the identification of effective sequences and combinations is of utmost importance. Major efforts should be directed to early identify and overcome resistance and to limit toxicity. The progress in the therapeutic management of NENs grows faster and the choice of the best approach should be based on randomized clinical trials, as well as on long-term, real-world data.

KEYWORDS:

• Carcinoid tumors
• chemotherapy
• everolimus
• immunotherapy
• neuroendocrine neoplasms
• lanreotide
• neuroendocrine tumors
• octreotide
• peptide receptor radionuclide therapy
• sunitinib
• target therapy
• therapy
• somatostatin analogs

Article highlights

• Neuroendocrine neoplasms (NENs) are heterogeneous malignancies mainly arising in the gastroenteropancreatic and bronchopulmonary systems, with steadily increasing incidence.

• Main therapeutic options in patients with NENs include somatostatin analogs (SSAs), targeted therapy with everolimus and sunitinib, peptide receptor radionuclide therapy (PRRT) and chemotherapy with variable indications and sequences.

• SSAs represent the cornerstone of treatment due to their efficacy in both symptom and tumor control, alongside with good safety profile, even in escalated doses. SSAs are the best candidate even in combination with other drugs in well and moderately differentiated NETs.

• Everolimus and sunitinib are the two currently approved targeted therapies, usually upon progression after SSAs.

• PRRT combines the diagnostic and therapeutic approach and allows to obtain both symptom and tumor control with promising results even in quality of life. The known safety could guarantee an anticipated placement in the therapeutic algorithm.

• Different regimens of chemotherapy are available, mainly in poorly differentiated or bulky and rapidly progressive NENs, but toxicity is higher than other therapeutic options.

• It is important to consider both data from clinical trials and real-world, as well as patients’ expectations and tumour characteristics to define the best therapeutic strategy in patients with NENs.

Declaration of interests

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.