Daniel Keizman1, Maya Ish-Shalom2, Avishay Sella3, Maya Gottfried2, Natalie Maimon2, Avivit Peer4, Hans Hammers5, Mario A Eisenberger5, Victoria Sinibaldi5, Victoria Neiman6, Eli Rosenbaum6, David Sarid7, Wilmosh Mermershtain8, Keren Rouvinov8, Raanan Berger9, Michael A Carducci5. 1. Department of Oncology, Meir Medical Center, Kfar Saba, Israel. Electronic address: danielkeizman@gmail.com. 2. Department of Oncology, Meir Medical Center, Kfar Saba, Israel. 3. Department of Oncology, Asaf Harofe Medical Center, Zerifin, Israel. 4. Department of Oncology, Rambam Medical Center, Haifa, Israel. 5. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD. 6. Department of Oncology, Rabin Medical Center, Petach-Tikva, Israel. 7. Department of Oncology, Tel Aviv Sourasky Medical center, Tel Aviv, Israel. 8. Department of Oncology, Soroka Medical Center, Beer-Sheva, Israel. 9. Department of Oncology, Sheba Medical Center, Tel Hashomer, Israel.
Abstract
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.
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 diabeticpatients with mRCC. PATIENTS AND METHODS: We performed a retrospective study of diabeticpatients 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 diabeticpatients 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 diabeticpatients with mRCC who are treated with sunitinib.
Authors: André Marquardt; Antonio Giovanni Solimando; Alexander Kerscher; Max Bittrich; Charis Kalogirou; Hubert Kübler; Andreas Rosenwald; Ralf Bargou; Philip Kollmannsberger; Bastian Schilling; Svenja Meierjohann; Markus Krebs Journal: Front Oncol Date: 2021-03-15 Impact factor: 6.244
Authors: Ondřej Fiala; Pavel Ostašov; Aneta Rozsypalová; Milan Hora; Ondřej Šorejs; Jan Šustr; Barbora Bendová; Ivan Trávníček; Jan Filipovský; Jindřich Fínek; Tomáš Büchler Journal: Cancer Manag Res Date: 2021-05-21 Impact factor: 3.989