IS2-2 - Biotherapy for Gepnets

Abstract

Somatostatin inhibits the synthesis and secretion of peptide hormones by a wide variety of neuroendocrine cells. Five subtypes of SSTRs have been reported, and these receptors are expressed in most NETs. Octreotide and Lanreotide are synthetic somatostatin analogs (SAs) that has high affinities for SSTRs 2 and 5. Octreotide binds mainly with SSTR 2 and improves symptoms of hormone excess. There have been many studies regarding the effects of SAs including octreotide on functional NETs; according to these studies, the mean response rate against signs and symptoms is 73%. The antitumor effect of octreotide LAR on well-differentiated metastatic NETs originating from the midgut was reported by the PROMID (placebo controlled, double-blind, prospective, randomized study of the effect of octreotide LAR in the control of tumor growth in patients with metastatic midgut tumors) study. Octreotide LAR significantly prolonged the TTP compared to the control (14.3 months vs. 6 months). The antitumor effects of SAs on PNETs were reported in various papers, which showed that tumor stabilization was observed in 40-80% of the study patients. In the NCCN guidelines, SAs are positioned as one of the treatment options (category 2B) for locally advanced/unresectable/metastatic PNETs. Very recently, the results of CLARINET (controlled study of lanreotide antiproliferative response in net) study in patients in gastrointestinal and PNETs showed that lanreotide autogel significantly prolonged PFS vs placebo. Pasireotide (SOM230) has affinities for SSTRs 1, 2, 3, and 5, and it is expected to elicit a stronger antitumor effect than octreotide. Currently, global randomized comparative phase II studies (cooperative studies) of pasireotide LAR and everolimus combination therapy and everolimus monotherapy in patients with advanced PNETs (NET G1/G2) are underway. In this symposium, the recent advances of biotherapy for GEPNETs are reviewed and future therapeutic strategy will be discussed.