Somatostatin Receptor Ligands

Specific Drugs in this Class

  • Octreotide long-acting (LAR)
  • Lanreotide
  • Pasireotide

Indications

Second or third-line therapy to control the metabolic effects of acromegaly, Cushing’s disease, and TSH-producing pituitary adenomas, in patients who did not achieve a biochemical remission after surgery and/or radiation therapy.

Effectiveness

  • IGF-1 normalization in patients with acromegaly: octreotide LAR ~ 25%, pasireotide ~ 40%.
  • UFC normalization in patients with Cushing’s: pasireotide ~ 40%.

Side Effects

  • Gallbladder stones/sludge.
  • Abdominal discomfort/diarrhea.
  • Hyperglycemia +/- prediabetes/diabetes (octreotide LAR ~ 20%, pasireotide ~ 60%).

Resistance to SRLs

Approx 10% of GH-producing adenomas are considered “resistant” to treatment with SRLs. Possible predictors of resistance are:

  • Younger age at diagnosis.
  • Sparsely granulated adenomas.
  • Aryl hydrocarbon receptor-interacting protein (AIP) mutations.
  • Lack of SSTR2 expression
  • High Ki67 proliferation index

Alternatives

In patients who do not respond to SRLs, consider:

  • Switching from octreotide or lenreotide to pasireotide.
  • Pegvisomant, either alone or in combination with an SRL (acromegaly only).
  • Cabergoline in combination with an SRL (acromegaly or TSH-producing adenomas).

Also consider radiation therapy or repeat surgery, if resectable.

References

  • Lim DST, Fleseriu M. The role of combination medical therapy in the treatment of acromegaly. Pituitary (2017) 20:136–148.
  • Melmed S, Casanueva FF, Klibanski A, Bronstein MD, Chanson P, Lamberts SW, Strasburger CJ, Wass JAH, Giustina A. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary (2013) 16:294–302.
  • Colao A, Bronstein MD, Freda P, Gu F, Shen CC, Gadelha M, Fleseriu M, van der Lely AJ, Farrall AJ, Hermosillo Reséndiz K, Ruffin M, Chen Y, Sheppard M. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. JCEM. 2014 Mar;99(3):791-9.
  • Lacroix A, Gu F, Gallardo W, Pivonello R, Yu Y, Witek P, Boscaro M, Salvatori R, Yamada M, Tauchmanova L, Roughton M, Ravichandran S, Petersenn S, Biller BMK, Newell-Price J. Efficacy and safety of once-monthly pasireotide in Cushing’s disease: a 12 month clinical trial. Lancet Diabetes Endocrinol. 2018 Jan;6(1):17-26
  • Colao A, Petersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Schoenherr U, Mills D, Salgado LR, Biller BM. Pasireotide B2305 Study Group. A 12-month phase 3 study of pasireotide in Cushing’s disease. NEJM. 2012 Mar 8;366(10):914-24.