What is the role of Lancreotide (Somatostatin analogue) in treating acromegaly or gastroenteropancreatic neuroendocrine tumors (GEP-NETs)?

Role of Lanreotide in Treating Acromegaly and GEP-NETs

Lanreotide is a first-line somatostatin analog indicated for the treatment of acromegaly, unresectable gastroenteropancreatic neuroendocrine tumors (GEP-NETs), and carcinoid syndrome, with proven efficacy for both symptom control and tumor growth inhibition. 1, 2

Mechanism of Action and Formulations

• Lanreotide is an octapeptide analog of natural somatostatin with high affinity for human somatostatin receptors (SSTR) 2 and 5, which is the primary mechanism responsible for growth hormone inhibition and neuroendocrine tumor control 1
• Available as a long-acting depot formulation (Somatuline Depot) administered as a deep subcutaneous injection every 4 weeks, with standard doses of 60,90, or 120 mg 3, 1
• Forms a drug depot at the injection site, with a mean absolute bioavailability of 73.4-78.4% depending on dose 1

Clinical Applications in Acromegaly

• FDA-approved for long-term treatment of acromegalic patients who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy 1
• Primary pharmacodynamic effect is reduction of GH and/or IGF-1 levels, enabling normalization of levels in acromegalic patients 1
• May be beneficial in patients with paraneoplastic acromegaly associated with ectopic secretion of growth hormone-releasing hormone (GHRH) 3

Clinical Applications in GEP-NETs

• FDA-approved for treatment of adult patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic GEP-NETs to improve progression-free survival 1
• Recommended by the National Comprehensive Cancer Network for both symptom control and anti-tumor effects in patients with neuroendocrine tumors 2
• Standard of care for symptomatic treatment of NETs, with long-acting formulations providing significant improvement in quality of life 3

Dosing and Administration

• Standard dosing for GEP-NETs is 120 mg every 4 weeks 2
• Patients should generally be started on lower doses with treatment up-titrated to achieve stabilization 3
• For breakthrough symptoms, shortening the administration interval from 4 to 3 weeks may be considered 3
• Dose optimization provides additional biochemical control in patients inadequately controlled with conventional starting doses 4

Efficacy in GEP-NETs

• The CLARINET study demonstrated that lanreotide significantly prolonged progression-free survival in patients with GEP-NETs, with an estimated PFS of 32.8 months 2
• In the PROMID trial, somatostatin analogs demonstrated prolonged progression-free survival in patients with metastatic NETs of midgut origin (14.3 months vs. 6 months with placebo) 3
• Stabilization of radiologically documented tumor progression has been demonstrated in 24-57% of patients with pancreatic NETs 3
• Ultra-high-dose lanreotide treatment has shown potential benefit in some patients with metastatic GEP-NETs refractory to conventional therapies 5

Symptom Control in Functional NETs

• FDA-approved for the treatment of adults with carcinoid syndrome to reduce the frequency of short-acting somatostatin analog rescue therapy 1
• Improvement of flushing and diarrhea is achieved in 70-80% of patients using long-acting formulations 3
• Effective for managing symptoms in patients with carcinoid syndrome, gastrinomas, and VIPomas 2
• Patients with carcinoid syndrome treated with lanreotide 120 mg every 4 weeks had reduced levels of urinary 5-hydroxyindoleacetic acid (5-HIAA) compared with placebo 1

Special Considerations

• Not recommended as first-choice agent for gastrinomas (PPIs are preferred) 3
• Often not effective in controlling hypoglycemia in patients with insulinoma unless the tumor is SSTR 2-positive 3
• May be beneficial in rare cases of PTHrP-secreting pancreatic NETs with hypercalcemia 3
• Can be beneficial in NETs patients with paraneoplastic Cushing's syndrome 3
• Role in non-functioning NETs was previously unclear 3, but more recent evidence supports its use for antiproliferative effects 2

Side Effects and Monitoring

• Common side effects include transient gastrointestinal issues (diarrhea, abdominal discomfort, flatulence, nausea) 3
• Can cause gallbladder abnormalities in approximately 26% of patients 2
• Produces a reduction and delay in postprandial insulin secretion, resulting in transient, mild glucose intolerance 2, 1
• May cause fat malabsorption and vitamin A and D malabsorption 2
• Patients should be monitored for symptom control and tumor response 2

Treatment Algorithm

1. For symptomatic patients with functional NETs:

   • Start with lanreotide 60-90 mg every 4 weeks and titrate up to 120 mg as needed 3, 2
   • For carcinoid syndrome refractory to standard dosing, consider shortening the injection interval to 3 weeks 3

2. For patients with unresectable, well- or moderately-differentiated GEP-NETs:

   • Initiate lanreotide 120 mg every 4 weeks for tumor growth control 2
   • Monitor for disease progression every 3-12 months 2

3. For acromegalic patients who have had inadequate response to surgery/radiotherapy:

   • Start with lanreotide 60-90 mg every 4 weeks and titrate based on GH/IGF-1 levels 1

4. For patients with carcinoid crisis prevention during procedures:

   • Use short-acting octreotide by intravenous administration before, during, and after procedures 6

Common Pitfalls and Caveats

• Co-administration of somatostatin analogs may reduce the sensitivity of somatostatin receptor scintigraphy imaging; schedule imaging toward the end of the dosing interval 3
• Not effective for grade 3 neuroendocrine carcinomas (NECs) regardless of the site of origin 3
• No indication for adjuvant therapy with somatostatin analogs in NET G1/G2 irrespective of primary tumor origin 3
• Patient preference studies indicate that factors surrounding injection administration are most influential in treatment experience, with lanreotide often preferred due to possibilities of extended dosing intervals and self/partner injection 7