Efficacy of Octreotide LAR, Lanreotide in Management of Carcinoid Tumors

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Octreotide is delivered via subcutaneous injections at first, to access patient tolerability.
Octreotide is delivered via subcutaneous injections at first, to access patient tolerability.

Patients with neuroendocrine tumors (NETs), formerly known as carcinoid tumors, may experience similar benefits when treated with long-acting, repeatable (LAR) octreotide and lanreotide, according to a review published in Seminars in Oncology. 

NETs are a group of heterogeneous neoplasms that originates from the endocrine and nervous systems, most frequently from the lung, small intestines, and rectum, and are characterized by the presence of secretory granules and slow growth. The first line therapy for NETs is resection but due to their insidious nature, may be unresectable or have metastasized at the time of diagnosis. For these cases, somatostatin analogues (SSAs) are the preferred agents not only due to efficacy in palliative treatment or symptom management, but also because of potential antitumor activity.

For patients with carcinoid symptoms, the optimal approach to therapy is administering subcutaneous (SC) injections of immediate-release (IR) octreotide twice daily for 3 to 7 days at the start of therapy to assess tolerability and titrate accordingly prior to administering the long-acting (LA) form. IR octreotide is typically administered to manage breakthrough symptoms even after LA octreotide for 10 to 14 days.

Octreotide LAR administered intramuscularly monthly allows patients with symptomatic NETs reach a steady-state of octreotide after 3 injections. Octreotide LAR is not only effective in symptom management, but also demonstrated that it may prolong time-to-progression (TTP).

In the PROMID study, the median TTP was 14.3 months and 6 months in the study arms receiving octreotide LAR and placebo, respectively (hazard ratio [HR], 0.34; 95% CI, 0.20-0.59; P =.000072). After 6 months, 66.7% and 37.2% of patients receiving octreotide LAR and placebo, respectively, had stable disease. The HR for overall survival (OS) was 0.81 (95% CI, 0.30-2.18).  The data from the study suggested that octreotide LAR may prolong TTP but not OS.

Generally, if the IR octreotide dose is 200 to 600 μg/day, octreotide LAR starting dose is 20 mg. If the IR octreotide dose is 750 to 1500 μg/day, octreotide LAR dose is 30 mg. The most commonly reported adverse events (AE) with octreotide include mild gastrointestinal disturbances and mild hyperglycemia.

The monthly cost of twice daily IR octreotide is approximately $1,440.00, and the monthly cost of octreotide LAR is $3,650.00.

Lanreotide, another SSA which is comparable to octreotide, demonstrated that it may prolong progression-free survival (PFS) among patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in the phase 3 CLARINET trial. Patients were randomly assigned to receive subcutaneous aqueous-gel lanreotide or placebo.

Patients receiving lanreotide did not reach median PFS compared with placebo-receiving patients, who achieved PFS of 18 months (P <.001); HR for progression or death was 0.47 (95% CI, 0.30-0.73). The estimated PFS rates at 24 months were 65% (95% CI, 54.0-74.1) in the lanreotide arm compared with 33% (95% CI, 23.0-43.3) in the placebo arm.

The most frequently reported AE for lanreotide are abdominal pain, bradycardia, and musculoskeletal pain.

The monthly cost of the standard recommended dose of lanreotide can potentially cost up to $8,400.00. 

The authors concluded that “in the near future, next generation SSAs alone or in combination with other therapies will hopefully provide more effective treatment options for NETs and an improved return on a patient's investment.” 

Reference

1. Enzler T, Fojo T. Long-acting somatostatin analogues in the treatment of unresectable/metastatic neuroendocrine tumors. Semin Oncol. 2017;44:141-56. doi: 10.1053/j.seminoncol.2017.07.001

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