SNFGE SNFGE
 
Thématique :
- Pancréas/Voies biliaires
Originalité :
Intermédiaire
Solidité :
A confirmer
Doit faire évoluer notre pratique :
Dans certains cas
 
 
Nom du veilleur :
Docteur Marine CAMUS DUBOC
Coup de coeur :
 
 
Gastroenterology
  2018/08  
 
  2018 Aug;155(2):479-489.e7.  
  doi: 10.1053/j.gastro.2018.04.010.  
 
  Metformin Use Is Associated With Longer Progression-Free Survival of Patients With Diabetes and Pancreatic Neuroendocrine Tumors Receiving Everolimus and/or Somatostatin Analogues  
 
  Pusceddu S, Vernieri C, Di Maio M, Marconcini R, Spada F, Massironi S, Ibrahim T, Brizzi MP, Campana D, Faggiano A, Giuffrida D, Rinzivillo M, Cingarlini S, Aroldi F, Antonuzzo L, Berardi R, Catena L, De Divitiis C, Ermacora P, Perfetti V, Fontana A, Razzore P, Carnaghi C, Davì MV, Cauchi C, Duro M, Ricci S, Fazio N, Cavalcoli F, Bongiovanni A, La Salvia A, Brighi N, Colao A, Puliafito I, Panzuto F, Ortolani S, Zaniboni A, Di Costanzo F, Torniai M, Bajetta E, Tafuto S, Garattini SK, Femia D, Prinzi N, Concas L, Lo Russo G, Milione M, Giacomelli L, Buzzoni R, Delle Fave G, Mazzaferro V, de Braud F  
  https://www.ncbi.nlm.nih.gov/pubmed/29655834  
 
 

Abstract

BACKGROUND & AIMS:

Metformin seems to have anticancer effects. However, it is not clear whether use of glycemia and metformin affect outcomes of patients with advanced pancreatic neuroendocrine tumors (pNETs). We investigated the association between glycemia and progression-free survival (PFS) of patients with pNETs treated with everolimus and/or somatostatin analogues, as well as the association between metformin use and PFS time.

METHODS:

We performed a retrospective analysis of 445 patients with advanced pNET treated at 24 medical centers in Italy from 1999 through 2015. Data on levels of glycemia were collected at time of diagnosis of pNET, before treatment initiation, and during treatment with everolimus (with or without somatostatin analogues), octreotide, or lanreotide. Diabetes was defined as prior or current use of glycemia control medication and/or fasting plasma glucose level ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5% (48 mmol/L), or a random sample of plasma glucose ≥ 200 mg/dL (11.1 mmol/L), with reported classic symptoms of hyperglycemia or hyperglycemic crisis. Patients were assigned to groups based on diagnosis of diabetes before or during antitumor therapy. PFS was compared between patients with vs without diabetes. Among patients with diabetes, the association between metformin use and PFS was assessed. We performed sensitivity and landmark analyses to exclude patients who developed diabetes while receiving cancer treatment and to exclude a potential immortal time bias related to metformin intake.

RESULTS:

PFS was significantly longer in patients with diabetes (median, 32.0 months) than without diabetes (median, 15.1 months) (hazard ratio for patients with vs without diabetes, 0.63; 95% confidence interval, 0.50-0.80; P = .0002). PFS of patients treated with metformin was significantly longer (median PFS, 44.2 months) than for patients without diabetes (hazard ratio for survival of patients with diabetes receiving metformin vs without diabetes, 0.45; 95% confidence interval, 0.32-0.62; P < .00001) and longer than for patients with diabetes receiving other treatments (median PFS, 20.8 months; hazard ratio, 0.49; 95% confidence interval, 0.34-0.69; P < .0001). In multivariable analysis, adjusted for other factors associated with outcomes, metformin was associated with longer PFS but level of glycemia was not. Metformin was associated with increased PFS of patients receiving somatostatin analogues and in those receiving everolimus, with or without somatostatin analogues. Sensitivity and landmark analyses produced similar results.

CONCLUSIONS:

In a retrospective study of patients with pNETs, we found a significant association between metformin use and longer PFS.

 

 
Question posée
 
Plusieurs études suggèrent des effets anticancéreux à la metformine, antidiabétique oral de la famille des biguanides. Cette étude s’est intéressé aux effets de la metformine chez des patients atteints de tumeurs neuroendocrines pancréatiques non résécables (PNETs). Dans cette étude portant sur 445 patients inclus de 1999 à 2015 dans 24 centres italiens, les auteurs ont étudié l'association entre glycémie et survie sans progression (progression-free survival-PFS) des patients présentant des PNETs bien différenciées traitées par des analogues de l'évérolimus et/ou par somatostatine, ainsi que l'association entre la prise de metformine et la PFS.
 
Question posée
 
Cette étude, portant sur 209 non diabétiques et 236 diabétiques dont 112 (25%) recevait la metformine suggère une association significative entre la prise de la metformine et une PFS plus longue chez les patients diabétiques atteints de PNETs. En analyse multivariée, ajustée pour tenir compte des autres facteurs associés, la metformine était associée à une PFS plus longue, mais pas le niveau de glycémie. La metformine était associée à une augmentation de la PFS chez les patients recevant des analogues de la somatostatine et chez ceux recevant de l'évérolimus, avec ou sans analogues de la somatostatine.
 
Commentaires

Cette étude présente cependant plusieurs limites: un design rétrospectif et l’absence de standardisation sur la dose et le schéma de prise de la metformine.

La metformine pourrait avoir des effets antitumoraux dans le traitement des patients atteints de pNETs avancé. Sur ces bases, deux études de phase II sont en cours pour approfondir ces résultats préliminaires.

 
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