What is lanreotide?

Lanreotide: A Somatostatin Analogue for Neuroendocrine Tumors

Lanreotide is a synthetic octapeptide somatostatin analogue used primarily for the treatment of neuroendocrine tumors (NETs), with proven efficacy in controlling hormone-related symptoms and tumor growth in patients with gastroenteropancreatic NETs. 1

Mechanism of Action

• Lanreotide is a synthetic cyclical octapeptide analog of the natural hormone somatostatin with a molecular weight of 1096.34 (base) 1
• It has high affinity for human somatostatin receptors (SSTR) 2 and 5, with reduced binding affinity for SSTR 1,3, and 4 1
• Like somatostatin, lanreotide inhibits various endocrine, neuroendocrine, exocrine, and paracrine functions 1
• The primary pharmacodynamic effect is inhibition of hormone secretion, particularly in hormone-producing NETs 1

Clinical Applications

Neuroendocrine Tumors

• Indicated for patients with unresectable, well to moderately differentiated, locally advanced or metastatic gastroenteropancreatic NETs 2
• Used for both symptom control and anti-tumor effects in patients with NETs 2, 3
• The CLARINET study demonstrated significant improvement in progression-free survival (PFS) with lanreotide compared to placebo (not reached vs 18 months; HR, 0.47; P<0.001) 2
• Shares the same mechanism of action as octreotide, making both appropriate options for tumor control 2

Hormone-Related Symptom Control

• Effective for managing symptoms in patients with carcinoid syndrome, gastrinomas, and VIPomas 2
• Reduces levels of urinary 5-hydroxyindoleacetic acid (5-HIAA) in patients with carcinoid syndrome 1
• Inhibits postprandial secretion of pancreatic polypeptide, gastrin, and cholecystokinin 1

Formulation and Administration

• Available as SOMATULINE DEPOT, a prolonged-release formulation for deep subcutaneous injection 1
• Comes in three strengths: 60 mg/0.2 mL, 90 mg/0.3 mL, and 120 mg/0.5 mL 1
• Standard dosing for NETs is 120 mg every 4 weeks 2
• Administered as a deep subcutaneous injection, unlike octreotide LAR which requires intramuscular administration 4
• Available in a convenient pre-filled syringe 5

Efficacy Data

• In the CLARINET study, lanreotide significantly prolonged progression-free survival in patients with gastroenteropancreatic NETs 2
• Subsequent data from the open-label extension of the CLARINET study estimated PFS in patients treated with lanreotide at 32.8 months 2
• Tumor shrinkage has been observed in 73% of patients with acromegaly, with mean tumor volume decrease of 44% 6
• Effectively controls both growth hormone and insulin-like growth factor-I levels in acromegaly 5

Side Effects and Safety Profile

• Generally well tolerated with low rates of treatment discontinuation 7
• Most common adverse events are mild to moderate transient gastrointestinal symptoms 5, 7
• Can cause gallbladder abnormalities in approximately 26% of patients 2
• May produce a reduction and delay in postprandial insulin secretion, resulting in transient, mild glucose intolerance 1
• Inhibits gallbladder contractility and bile secretion 1
• Can cause fat malabsorption and vitamin A and D malabsorption 8

Special Populations

Renal Impairment

• No effect on total clearance observed in patients with mild to moderate renal impairment receiving 120 mg 1
• Patients with severe renal impairment have not been adequately studied 1

Hepatic Impairment

• Has not been studied in patients with hepatic impairment for NET indications 1
• For acromegaly, patients with moderate or severe hepatic impairment should receive a starting dose of 60 mg 1

Elderly Patients

• No overall differences in safety or effectiveness observed between elderly and younger patients 1
• Dose selection should be cautious, usually starting at the low end of the dosing range 1

Clinical Considerations and Algorithm

1. For asymptomatic patients with unresectable NETs, low tumor burden, and stable disease:

   • Consider observation with marker assessment and imaging every 3-12 months 2
   • Treatment with lanreotide can be considered to control tumor growth 2

2. For symptomatic patients with unresectable disease or clinically significant tumor burden:

   • Initiate lanreotide 120 mg every 4 weeks 2
   • Monitor for symptom control and tumor response 2

3. For patients with carcinoid syndrome:

   • Lanreotide is effective for symptom control 2
   • Consider cardiology consultation and echocardiogram to assess for carcinoid heart disease 2

Comparison with Other Treatments

• Lanreotide and octreotide share the same mechanism of action 2
• Lanreotide offers the advantage of subcutaneous administration versus intramuscular for octreotide LAR 5, 4
• For tumor control in NETs, both lanreotide and octreotide are appropriate options 2
• Other treatment options for advanced NETs include biologically targeted agents (everolimus or sunitinib) or cytotoxic chemotherapy 2

Common Pitfalls and Caveats

• Somatostatin receptors are present in 70-95% of NETs but only in about half of insulinomas 8
• Lanreotide is not effective in controlling hypoglycemia in most patients with insulinoma (only effective in SSTR 2-positive cases) 8
• For optimal imaging with somatostatin receptor scintigraphy, short-acting somatostatin analogues should be withdrawn 24-48 hours before imaging 8
• Glucose metabolism may deteriorate in approximately 12% of patients 6