Metformin Use and the Outcome of Metastatic Renal Cell Carcinoma Treated with Sunitinib or Pazopanib

Ondřej Fiala; Pavel Ostašov; Aneta Rozsypalová; Milan Hora; Ondřej Šorejs; Jan Šustr; Barbora Bendová; Ivan Trávníček; Jan Filipovský; Jindřich Fínek; Tomáš Büchler

doi:10.2147/CMAR.S305321

Metformin Use and the Outcome of Metastatic Renal Cell Carcinoma Treated with Sunitinib or Pazopanib

Cancer Manag Res. 2021 May 21:13:4077-4086. doi: 10.2147/CMAR.S305321. eCollection 2021.

Authors

Ondřej Fiala^{1

2}, Pavel Ostašov³, Aneta Rozsypalová⁴, Milan Hora⁵, Ondřej Šorejs^{1

2}, Jan Šustr¹, Barbora Bendová⁵, Ivan Trávníček⁵, Jan Filipovský⁶, Jindřich Fínek¹, Tomáš Büchler⁴

Affiliations

¹ Department of Oncology and Radiotherapy, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.
² Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech, Czech Republic.
³ Laboratory of Tumor Biology and Immunotherapy, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech, Czech Republic.
⁴ Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic.
⁵ Department of Urology, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.
⁶ 2nd Department of Internal Medicine, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.

Abstract

Background: The anticancer properties of metformin have been suggested in numerous experimental studies and several retrospective clinical studies show that its use is associated with improved outcome of patients with cancer. However, limited data are available for patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy. The aim of this retrospective study was to assess the impact of the metformin use on survival of mRCC patients treated with sunitinib or pazopanib.

Methods: Clinical data from 343 patients with mRCC treated with sunitinib or pazopanib in the first line were analyzed. Progression-free survival (PFS) and overall survival (OS) were compared according to the use of metformin.

Results: The median PFS and OS for patients using metformin was 31.1 (95% CI 20.6-35.1) and 51.6 (95% CI 44.7-NR) months compared to 9.3 (95% CI 8.0-12.0) and 22.4 (95% CI 19.4-26.8) months for patients not using metformin (p<0.0001 and p=0.0002, respectively). Cox multivariate analysis shows that the use of metformin remains a significant factor for PFS (HR=0.55 [95% CI 0.343-0.883], p=0.013) and also for OS (HR=0.45 [95% CI 0.256-0.794], p=0.006).

Conclusion: The present study results suggest that the use of metformin was associated with favorable outcome of mRCC patients treated with sunitinib or pazopanib.

Keywords: metformin; outcome; pazopanib; renal cell carcinoma; sunitinib; tyrosine kinase inhibitors.

Grants and funding

This study was supported by the Institutional Research Fund of University Hospital Plzen, FN 00669806 and by the Charles University Research Fund (Progres Q39), by the European Regional Development Fund-Project “Application of Modern Technologies in Medicine and Industry” (No. CZ.02.1.01/0.0/0.0/17_048/0007280) and by the grant of Ministry of Health of the Czech Republic - AZV NV19-08-00250, and by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 856620.