(Ir)relevance of metformin treatment in patients with metastatic pancreatic cancer: an open-label, randomized phase 2 trial
Mené en Italie sur 60 patients atteints d'un cancer métastatique du pancréas, cet essai randomisé de phase II évalue l'efficacité, du point de vue de la survie sans progression à 6 mois, de l'ajout de metformine à une chimiothérapie de référence
Objective. We aimed to assess the safety and efficacy of metformin for treating patients with metastatic pancreatic cancer and to identify endocrine and metabolic phenotypic features or tumor molecular markers associated with sensitivity to metformin antineoplastic action. Research Design and Methods. We designed an open-label, randomized, phase II trial to assess the efficacy of adding metformin to a standard systemic therapy with cisplatin, epirubicin, capecitabine, gemcitabine (PEXG) in patients with metastatic pancreatic cancer. Patients aged 18 years or older with metastatic pancreatic cancer were randomly assigned (1:1) to receive PEXG every 4 weeks in combination or not with 2 grams oral metformin daily. The primary endpoint was 6-months progression-free survival (PFS-6) in the intention-to-treat population. Results. Between August 2010 and January 2014 we randomly assigned 60 patients to receive PEXG with (n=31) or without metformin (n=29). At the preplanned interim analyses the study was ended for futility. PFS-6 was 52% (33-69) in the control group and 42% (24-59) in the metformin group (p=0.61). Furthermore, there was no difference in disease-free survival and overall survival between groups. Despite endocrine metabolic modifications were induced by metformin, there was no correlation with the outcome. SNP rs11212617 predicted glycemic response, but not tumor response to metformin. Gene expression on tumor tissue did not predict tumor response to metformin. Conclusion. Addition of metformin at the dose commonly used in diabetes did not improve outcome in patients with metastatic pancreatic cancer treated with standard systemic therapy.