Lead Investigator: Chiara Alessandra Cella, Istituto Europeo di Oncologia
Title of Proposal Research: Addressing the synergistic effect of metformin in patients with Pancreatic neuroendocrine tumors treated with sunitinib: a post-hoc analysis from the main pivotal trials.
Vivli Data Request: 7874
Funding Source: None
Potential Conflicts of Interest: CAC reports personal fees from BMS and Leo Pharma; and a research grant from IPSEN (institutional).
Any potential conflicts of interest will be declared in subsequent publication.
Dr. Fazio received personal fees from AAA, Hutchinson MediPharma, Merck, Novartis; has financial interest with 4SC, Astellas, Beigene, FIBROGEN, Incyte, IPSEN, MSD and NUCANA; and has received research grant form IPSEN (institutional).
Any potential conflicts of interest will be declared in subsequent publication.
Summary of the Proposed Research:
Neuroendocrine neoplasms (NENs) are a type of abnormal and excessive growth of tissue, accounting for about 0.5% of all newly diagnosed malignancies. The worldwide incidence, which is on the rise, possibly due to improved awareness, is approximately 5.86/100,000 per year with a prevalence in the United States estimated around <200,000, which makes it an orphan disease. Pancreatic neuroendocrine neoplasm (Pan-NENs), represent less than 3% of primary pancreatic tumors and involve the pancreatic islet cell, a pancreatic cell that produces hormones (e.g., insulin and glucagon) that are secreted into the bloodstream to help control the level of glucose (sugar) in the blood (also called islet of Langerhans). The mainstay of treatment is surgery with curative intent, if possible. When surgery has no indication, chronic medical management is required. Among the approved options, sunitinib (SUN) represents a cornerstone in the therapeutical strategy on Pan-NENs, having showed a progression-free survival (PFS) doubling rate over placebo. PFS refers to the time during which a patient shows no signs or symptoms of the growth or the spreading of a tumor. However, soon or later, the onset of intrinsic or acquired resistance still represents the limiting criteria for a durable response.
Metformin (MET) is one of the most popular oral glucose-lowering medications, widely considered to be the optimal initial therapy for patients with type 2 diabetes mellitus (DM2). Metformin has shown to exert an anti-tumor effect in solid tumors, including NENs. More in detail, MET has shown to inhibit tumor growth in Pan-NENs in preclinical models and is also associated with longer PFS in patients with Pan-NENs receiving everolimus, a drug used as an immunosuppressant to prevent rejection of organ transplants and as a targeted therapy in the treatment of several solid tumours. Additionally, MET has shown safety and efficacy in improving outcomes even when combined with sunitinib in renal cell carcinoma.
Neverthless, limited data are available on a possibile role of MET in patients with Pan-NENs treated with antiangiogenic targeted agents, like sunitinib.
Basically, the aim of this analysis is to evaluate if the association between the MET and SUN improves survival in patients with advanced Pan-NETs.
Requested Studies:
A Phase II Study Of The Efficacy And Safety Of SU011248 In Patients With Advanced Unresectable Neuroendocrine Tumor
Data Contributor: Pfizer Inc.
Study ID: NCT00056693
Sponsor ID: RTKC-0511-015
A Phase III Randomized, Double-Blind Study Of Sunitinib (SU011248, SUTENT) Versus Placebo In Patients With Progressive Advanced/Metastatic Well-Differentiated Pancreatic Islet Cell Tumors
Data Contributor: Pfizer Inc.
Study ID: NCT00428597
Sponsor ID: A6181111
Raymond E, Kulke MH, Qin S, Yu X, Schenker M, Cubillo A, Lou W, Tomasek J, Thiis-Evensen E, Xu JM, Croitoru AE, Khasraw M, Sedlackova E, Borbath I, Ruff P, Oberstein PE, Ito T, Jia L, Hammel P, Shen L, Shrikhande SV, Shen Y, Sufliarsky J, Khan GN, Morizane C, Galdy S, Khosravan R, Fernandez KC, Rosbrook B, Fazio N. Efficacy and Safety of Sunitinib in Patients with Well-Differentiated Pancreatic Neuroendocrine Tumours. Neuroendocrinology. 2018;107(3):237-245. doi: 10.1159/000491999. Epub 2018 Jul 10. PMID: 29991024.
Data Contributor: Pfizer Inc.
Study ID: NCT01525550