Antiproliferative Effect of Somatostatin Analogs – Data Analyses and Clinical Applications in the Context of the CLARINET Study

Abstract

Background: Somatostatin analogs (SSAs) are antisecretory agents that have been used to control hormonal syndromes associated with neuroendocrine tumors for more than 20 years. Recent phase III randomized, placebo controlled trials demonstrated their antiproliferative effects. The PROMID study showed that octreotide LAR (long‐acting repeatable) treatment had anti‐tumor effects. CLARINET, an international multicenter controlled study, provides new evidence that lanreotide has antiproliferative effects. Depot lanreotide significantly prolonged progression‐free survival among patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP‐NETs). Because GEP‐NETs are biologically diverse in terms of primary tumor site and functional status, preventing progression can be difficult. Aim: This review summarizes data supporting the role of SSAs, in particular lanreotide, as antiproliferative agents for the treatment of patients with GEP‐NETs. Conclusion: The CLARINET study is the most powerful (in sence of data, results, clinical aplication) randomized study of the antiproliferative effects of SSA in GEP‐NET patients. The median lanreotide‐associated progression‐free survival in the CLARINET core study or in open‐label extension study was 32.8 vs. 18 months for placebo. Thus, early treatment with lanreotide is expected to prolong progression‐free survival. Lanreotide is now recommended for the treatment of patients with well‐differentiated metastatic grade land grade 2 GEP‐NETs (i.e., those with a Ki‐67 proliferative index < 10%) located in the pancreas, small intestine, or in cases where the location of the primary tumor is unknown, regardless of the degree of liver involvement.