What is the treatment for a well-differentiated neuroendocrine tumor (NET)?

From the Guidelines

The treatment of well-differentiated neuroendocrine tumors (NETs) should prioritize somatostatin analogs, such as octreotide LAR or lanreotide, as first-line therapy for metastatic or unresectable disease, as they control hormone-related symptoms and slow tumor growth, as recommended by the most recent guidelines 1. The treatment approach for well-differentiated NETs depends on various factors including tumor location, stage, grade, and presence of symptoms.

• For localized disease, surgical resection is the primary treatment with curative intent.
• For metastatic or unresectable disease, somatostatin analogs like octreotide LAR (20-30 mg intramuscularly every 4 weeks) or lanreotide (120 mg subcutaneously every 4 weeks) are first-line treatments, as they control hormone-related symptoms and slow tumor growth.
• Targeted therapies such as everolimus (10 mg orally daily) or sunitinib (37.5 mg orally daily) may be used for progressive disease, as supported by studies demonstrating their efficacy in controlling tumor growth and improving progression-free survival 1.
• Peptide receptor radionuclide therapy (PRRT) with lutetium-177 dotatate (200 mCi intravenously every 8 weeks for 4 cycles) is effective for somatostatin receptor-positive tumors, offering a promising option for patients with advanced disease 1.
• Liver-directed therapies including embolization, chemoembolization, or radioembolization are options for liver-predominant metastases.
• Cytotoxic chemotherapy with temozolomide and capecitabine is typically reserved for pancreatic NETs or higher-grade tumors. Treatment selection is guided by tumor characteristics, disease burden, and patient factors, with the goal of controlling symptoms and disease progression while maintaining quality of life.
• A multidisciplinary evaluation is essential for optimal management of these complex tumors, incorporating expertise from oncology, surgery, radiology, and nuclear medicine to provide comprehensive care.
• The use of somatostatin analogs, targeted therapies, and PRRT is supported by recent studies and guidelines, emphasizing the importance of staying updated with the latest evidence-based recommendations for the management of well-differentiated NETs 1.

From the FDA Drug Label

Lanreotide Injection is indicated for the treatment of adult patients with unresectable, well or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival. The recommended dosage of Lanreotide Injection for well-differentiated neuroendocrine tumor is 120 mg administered every 4 weeks by deep subcutaneous injection 2. Key points:

• The treatment is for unresectable, well or moderately differentiated tumors.
• The goal is to improve progression-free survival.
• The dosage is the same for well-differentiated and moderately differentiated tumors.

From the Research

Treatment Options for Well-Differentiated Neuroendocrine Tumors

• Surgery is considered the best chance of cure for patients with well-differentiated neuroendocrine tumors, with tumor resection being the preferred approach when possible 3.
• For locally advanced or metastatic disease, treatment approaches can vary widely depending on the extent of disease and goals of therapy 3.
• Targeted therapies, such as everolimus and tyrosine kinase inhibitors, have been developed based on a better understanding of the biology of neuroendocrine tumors 3.
• Somatostatin analogues, such as octreotide and lanreotide, are a mainstay of treatment for well-differentiated neuroendocrine tumors, reducing secretory products and having antiproliferative effects on tumor cells 3, 4, 5, 6.
• Chemotherapy, including the combination of temozolomide and capecitabine, has a role in the treatment of well-differentiated neuroendocrine tumors, particularly for pancreatic neuroendocrine tumors 3, 7.

Role of Somatostatin Analogues

• Somatostatin analogues have been shown to have antiproliferative effects and inhibit tumor growth via the somatostatin receptor 2 (SSTR2) 5, 6.
• The PROMID and CLARINET trials demonstrated a statistically significant prolongation of time to progression/progression-free survival (TTP/PFS) with somatostatin analogue treatment compared to placebo 6.
• The combination of somatostatin analogues with peptide receptor radionuclide therapy (PRRT) has proven efficacy in small intestinal neuroendocrine tumors 6.

Treatment Outcomes for Well-Differentiated High-Grade Neuroendocrine Tumors

• The oral combination of capecitabine and temozolomide is considered a good option in the management of metastatic well-differentiated high-grade neuroendocrine tumors, with clinically meaningful efficacy and disease control 7.
• FOLFOX is another systemic option with reasonable efficacy, while peptide receptor radionuclide therapy seems to have some efficacy in these tumors 7.
• Platinum-etoposide has some activity in well-differentiated high-grade neuroendocrine tumors, but responses appear to be short-lived 7.