Lana Hamieh1, Rana R McKay1, Xun Lin2, Raphael B Moreira1, Ronit Simantov2, Toni K Choueiri3. 1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. 2. Pfizer Oncology, Pfizer Inc, New York, NY. 3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. Electronic address: Toni_Choueiri@dfci.harvard.edu.
Abstract
INTRODUCTION: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.
INTRODUCTION: 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. PATIENTS AND METHODS: 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. RESULTS: 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 diabeticpatients 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). CONCLUSION: 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: 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