Abstract 608P
Background
Preclinical studies have suggested that metformin has antitumor effects, likely due to blockage of mTOR pathway through AMPK and decreased insulin levels. A retrospective study showed that metformin combined with everolimus to treat related hyperglycemia offered longer progression-free survival (PFS) in patients (pts) with pancreatic neuroendocrine tumors (NET). Aim(s): To evaluate the efficacy and safety of metformin monotherapy in non-diabetic NET pts.
Methods
Single-arm phase II trial of metformin 850mg PO twice daily until progression or intolerance for non-diabetic pts with radiologically progressive metastatic G1 or G2 gastroenteropancreatic (GEP) NET (NCT02279758). The primary endpoint was disease control rate (DCR) by RECIST 1.1 at 6 months. Secondary endpoints were: clinical and radiological response rate, PFS, toxicity and variations in glycemia, glycated hemoglobin and peptide C kinetics at baseline and at every 90 days.
Results
From 2014 to 2019, 28 pts were enrolled: median age was 50 years, 53% was male, 84% had nonfunctional NET, 71% received metformin as their first treatment (those candidates for watchful wait), 86% had GEP NET,62% had G2 NET. At the time of last follow up, 26 pts presented progression. Thirteen pts (46%) presented DCR at 6 months, with a median PFS of 6,3 months (95% Confidence interval: 3,2 – 9.3). No pt presented objective response but one pt with refractory carcinoid syndrome had complete symptom relief, lasting for more than 4 years. The variation in the glycemic tests (glycemia, glycated hemoglobin, peptide C and insulin) was not associated with DCR at 6 months. Diarrhea was the most common adverse event: G1/2 in 17% and Grade 3 or 4 in 10%.
Conclusions
Metformin monotherapy offers modest antitumor activity in NET and high frequency of diarrhea, and should not be tested in further trials as an isolated treatment.
Clinical trial identification
NCT02279758.
Editorial acknowledgement
Legal entity responsible for the study
Instituto do Câncer do Estado de São Paulo - ICESP, São Paulo, Brazil.
Funding
Has not received any funding.
Disclosure
J. Glasberg: Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Ipsen. R.S.P. Riechelmann: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self): Ipsen. All other authors have declared no conflicts of interest.