Increased Development of Targeted Therapies in the Neuroendocrine Tumors Pipeline Promises a Shift in the Standard of Care

GlobalData Healthcare 14th August 2020 (Last Updated August 14th, 2020 15:55)
Increased Development of Targeted Therapies in the Neuroendocrine Tumors Pipeline Promises a Shift in the Standard of Care

Neuroendocrine tumors (NETs) are a group of rare, heterogeneous tumors that can develop sporadically in many different organs of the body. They arise from specialized cells of the nervous and endocrine system called the neuroendocrine cells. The majority of NETs occur in the gastrointestinal tract followed by the lungs, pancreas, and thymus.

In about 15% of cases, the primary site of NETs cannot be determined. The overall prognosis of NET patients varies according to the stage at diagnosis, histologic classification, and primary site of the tumor. However, due to the asymptomatic nature of early-stage NETs and the presence of symptoms associated with endocrine-related syndromes in functional NETs, NET patients are often misdiagnosed, or diagnosed at advanced or metastatic stages. This results in poorer prognosis due to the challenging treatment and limited treatment options.

Most early-stage, localized NETs are managed by surgery, but systemic therapy is the standard of care for unresectable tumors and advanced, metastatic stages. In the eight major markets (8MM: US, France, Germany, Italy, Spain, UK, Japan, and China), the somatostatin analogs (SSAs), Novartis’ Sandostatin (octreotide) and Ipsen’s Somatuline (lanreotide), have been the long-time standard of care for the treatment of gastroenteropancreatic (GEP) NETs and their symptoms. Recently, the approval of the targeted therapies, Novartis’ Afinitor (everolimus) and Pfizer’s Sutent (sunitinib), has provided more promising treatment options to improve outcomes for GEP and lung NETs. Further, Novartis’ Lutathera (lutetium Lu 177-dotatate) and Progenics Pharmaceuticals’ Azedra (iobenguane I 131 [131I-mIBG]) are peptide receptor radionuclide therapies (PRRT), which allow visualization, diagnosis, and treatment of GEP-NET patients refractory to SSAs, and pheochromocytoma/paraganglioma tumors, respectively. Merck’s Intron A (interferon alfa 2b) and various cytotoxic chemotherapy options are also available and generally used if hormonal or targeted therapies are inefficient, and in the absence of other therapeutic options, due to their limited efficacy and high side-effect profiles.

Recently, there has been an increase in the incidence of NETs, which has been attributed to earlier and improved diagnosis, and increased awareness of NETs. Access to innovative technologies and medicines in NETs is a major global challenge, with inequalities arising among countries, and the availability of effective therapies is a huge unmet need. Targeted therapies now represent 66% of new products in the late-stage (Phase II and Phase III) pipeline for NETs in the 8MM, with the rest being chemotherapies, suggesting an impending shift in the standard of care. Protein kinase inhibitors dominate the targeted therapy pipeline at 52%, followed by immune checkpoint inhibitors (33%), and PRRTs (14%). However, concerns have been raised surrounding the potential high costs of these therapies, which may limit their availability to patients. Further, only a third of these clinical trials for targeted therapies are industry-sponsored, with the rest being institution- or investigator-led, posing the question about whether it is feasible for these therapies to enter the market for the treatment of NET patients in the next five to ten years.

The figure above displays the distribution of active Phase II and Phase III clinical trials by therapeutic class in the current development pipeline for NETs in the 8MM.