Metformin Use and Outcome of Sunitinib Treatment in Patients With Diabetes and Metastatic Renal Cell Carcinoma

Daniel Keizman, Maya Ish-Shalom, Avishay Sella, Maya Gottfried, Natalie Maimon, Avivit Peer, Hans Hammers, Mario A. Eisenberger, Victoria Sinibaldi, Victoria Neiman, Eli Rosenbaum, David Sarid, Wilmosh Mermershtain, Keren Rouvinov, Raanan Berger, Michael A. Carducci

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

We analyzed the effect of metformin use on sunitinib treatment outcome in diabetic patients with metastatic renal cell carcinoma. In metformin users versus nonusers, clinical benefit was 96% versus 84% (P = .054), median progression-free survival was 15 versus 11.5 months (P = .1), and median overall survival (OS) was 32 versus 21 months (P = .001). In multivariate analyses of the entire patient cohort, metformin use was associated with OS. Background Although studies in several cancer types suggest that metformin has antitumor activity, its effect on the outcome of targeted therapies in metastatic renal cell carcinoma (mRCC) is poorly defined. We aimed to analyze the effect of metformin use on the outcome of sunitinib treatment in diabetic patients with mRCC. Patients and Methods We performed a retrospective study of diabetic patients with mRCC, who were treated with sunitinib in 8 centers across 2 countries. Patients were divided into metformin users and nonusers. The effect of metformin use on response rate, progression-free survival (PFS), and overall survival (OS), was tested. Furthermore, univariate and multivariate analyses of the association between clinicopathologic factors and metformin use, and outcome were performed using the entire patient cohort. Results Between 2004 and 2014, 108 diabetic patients with mRCC were treated with sunitinib. There were 52 metformin users (group 1) and 56 nonusers (group 2). The groups were balanced regarding clinicopathologic factors. Clinical benefit (partial response + stable disease) in group 1 versus 2 was 96% versus 84% (P = .054). Median PFS was 15 versus 11.5 months (P = .1). Median OS was 32 versus 21 months (P = .001). In multivariate analyses of the entire patient cohort (n = 108), factors associated with PFS were active smoking and pretreatment neutrophil to lymphocyte ratio > 3. Factors associated with OS were metformin use (hazard ratio, 0.21; P < .0001), Heng risk, active smoking, liver metastases, and pretreatment neutrophil to lymphocyte ratio > 3. Conclusion Metformin might improve the OS of diabetic patients with mRCC who are treated with sunitinib.

Original languageEnglish (US)
Pages (from-to)420-425
Number of pages6
JournalClinical Genitourinary Cancer
Volume14
Issue number5
DOIs
StatePublished - Oct 1 2016

Keywords

  • Metastatic Renal Cell Carcinoma
  • Metformin
  • Outcome
  • Sunitinib

ASJC Scopus subject areas

  • Oncology
  • Urology

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    Keizman, D., Ish-Shalom, M., Sella, A., Gottfried, M., Maimon, N., Peer, A., Hammers, H., Eisenberger, M. A., Sinibaldi, V., Neiman, V., Rosenbaum, E., Sarid, D., Mermershtain, W., Rouvinov, K., Berger, R., & Carducci, M. A. (2016). Metformin Use and Outcome of Sunitinib Treatment in Patients With Diabetes and Metastatic Renal Cell Carcinoma. Clinical Genitourinary Cancer, 14(5), 420-425. https://doi.org/10.1016/j.clgc.2016.04.012