What is the role of Lanreotide (Somatostatin analogue) in managing a grade 2 pancreatic neuroendocrine tumor (PNET) with liver metastases, discovered 3 months post-resection, with Dotatate (Somatostatin receptor scintigraphy) avid regions?

From the Guidelines

Lanreotide is an appropriate treatment for your situation with a resected grade 2 pancreatic neuroendocrine tumor (NET) that has now shown evidence of liver metastases on dotatate imaging. The standard dosing is typically 120 mg administered as a deep subcutaneous injection every 4 weeks, as seen in studies such as the CLARINET study 1. This medication is a somatostatin analog that works by binding to somatostatin receptors on the tumor cells, which helps control tumor growth and can manage symptoms if your tumor is functional (hormone-producing). For metastatic pancreatic NETs like yours, lanreotide has been shown to significantly delay disease progression, with results from the CLARINET study showing an improved progression-free survival (PFS) compared with placebo (PFS not reached vs 18 months, respectively; HR, 0.47; 95% CI, 0.30–0.73; P<.001) 1. Common side effects include:

• injection site reactions
• abdominal discomfort
• diarrhea
• gallstones You should continue regular imaging follow-ups every 3-6 months to monitor treatment response. Blood tests to check tumor markers like chromogranin A and specific hormones may be recommended. Lanreotide may cause mild glucose abnormalities, so blood sugar monitoring is important, especially if you have diabetes. The treatment is typically long-term and will continue as long as it's controlling the disease and you're tolerating it well. It's also important to consider the management of locoregional unresectable and/or metastatic NETs of the pancreas, as discussed in the guidelines 1, which may include surgical excision of both the primary tumor and liver metastases, noncurative debulking surgery, or other systemic options.

From the FDA Drug Label

1. 2 Gastroenteropancreatic Neuroendocrine Tumors 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.

2 DOSAGE AND ADMINISTRATION 2. 1 Recommended Dosage Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) The recommended dosage of Lanreotide Injection is 120 mg administered every 4 weeks by deep subcutaneous injection.

The patient has a grade 2 pancreatic neuroendocrine tumor (NET) that was resected, and dotatate avid regions in the liver were discovered 3 months after resection. Lanreotide was prescribed for use every 4 weeks.

• The indication for Lanreotide in this case is 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 2.
• The recommended dosage of Lanreotide Injection for GEP-NETs is 120 mg administered every 4 weeks by deep subcutaneous injection 2. Given that the tumor was resected, but metastatic disease is present in the liver, Lanreotide may be used to improve progression-free survival. However, the fact that the primary tumor was resected may affect the treatment approach, and the decision to use Lanreotide should be made on a case-by-case basis, considering the individual patient's circumstances. 2

From the Research

Lanreotide Treatment for Pancreatic Neuroendocrine Tumors

• Lanreotide is a somatostatin analogue (SSA) used in the treatment of neuroendocrine tumors (NETs), including pancreatic NETs 3, 4.
• The treatment of NETs typically involves surgery, but for inoperable or metastatic disease, SSAs like lanreotide are used for symptom management and tumor control 3, 4.
• In the case of a grade 2 pancreatic NET that was resected, the discovery of dotatate avid regions in the liver 3 months post-resection indicates the presence of metastatic disease 5, 6.
• Lanreotide prescribed every 4 weeks may help control tumor growth and manage symptoms in this patient, as evidenced by studies showing the antiproliferative effects of SSAs in NETs 4, 7.

Efficacy and Safety of Lanreotide

• The CLARINET trial demonstrated a statistically significant prolongation of time to progression/progression-free survival (TTP/PFS) with lanreotide treatment compared to placebo in patients with NETs 4.
• A systematic review of SSA treatment in patients with MEN1-related pancreatic NETs found an overall response rate of 88.3% and a favorable safety profile with lanreotide 7.
• The use of lanreotide in combination with other treatment modalities, such as peptide receptor radionuclide therapy (PRRT), may also be effective in managing NETs 4, 5.

Somatostatin Receptors and Pancreatic NETs

• Somatostatin receptors (SSTRs) are widely expressed in pancreatic NETs and can be targeted by SSAs like lanreotide for diagnostic and therapeutic purposes 6.
• The expression of SSTRs in pancreatic NETs has been shown to have clinical significance in diagnosis, treatment, and prognostic prediction 6.