title: Effect of Metformin Use on Survival Outcomes in Patients With Metastatic Renal Cell Carcinoma.
abstract: Observational studies have suggested that metformin use is associated with favorable outcomes in several cancers. For renal cell carcinoma (RCC), data have been limited. Therefore, we investigated the effect of metformin on survival in metastatic RCC (mRCC) using a large clinical trial database.
  
  
  
  We conducted a retrospective analysis of patients with mRCC in phase II and III clinical trials. The overall survival (OS) in metformin users was compared with that of users of other antidiabetic agents and those not using antidiabetic agents. Progression-free survival, objective response rate, and adverse events were secondary endpoints. Subgroup analyses were conducted after stratifying by class of therapy, type of vascular endothelial growth factor tyrosine kinase inhibitors, and International Metastatic RCC Database Consortium (IMDC) risk groups.
  
  
  
  We identified 4736 patients with mRCC, including 486 with diabetes, of whom 218 (4.6%) were taking metformin. Metformin use did not affect OS when compared with users of other antidiabetic agents or those without diabetes. Furthermore, metformin use did not confer an OS advantage when stratified by class of therapy and IMDC risk group. However, in diabetic patients receiving sunitinib (n = 128), metformin use was associated with an improvement in OS compared with users of other antidiabetic agents (29.3 vs. 20.9 months, respectively; hazard ratio, 0.051; 95% confidence interval, 0.009-0.292; P = .0008).
  
  
  
  In the present study, we found a survival benefit for metformin use in mRCC patients treated with sunitinib. Clinical and preclinical studies are warranted to validate our results and guide the use of metformin in the clinic.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Lana
authors.initials: L
authors.lastname: Hamieh
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Rana R
authors.initials: RR
authors.lastname: McKay
authors.affiliation: Pfizer Oncology, Pfizer Inc, New York, NY.
authors.forename: Xun
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Raphael B
authors.initials: RB
authors.lastname: Moreira
authors.affiliation: Pfizer Oncology, Pfizer Inc, New York, NY.
authors.forename: Ronit
authors.initials: R
authors.lastname: Simantov
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. Electronic address: Toni_Choueiri@dfci.harvard.edu.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077210:Sunitinib; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D008687:Metformin; D000077210:Sunitinib
keywords: Diabetes; Kidney cancer; Prognosis; Sunitinib; Targeted therapy