Concomitant Use of Statins, Metformin, or Proton Pump Inhibitors in Patients with Advanced Renal Cell Carcinoma Treated with First-Line Combination Therapies

Background: Drug–drug interactions are a major concern in oncology and may potentially affect the outcome of patients with cancer. Objective: In this study, we aimed to determine whether the concomitant use of statins, metformin, or proton pump inhibitors affects survival in patients with metastatic renal cell carcinoma treated with first-line combination therapies. Methods: Medical records of patients with documented metastatic renal cell carcinoma between January 2016 and November 2021 were reviewed at 17 participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. Patients were assessed for overall survival, progression-free survival, and overall clinical benefit. Univariate and multivariate analyses were conducted to explore the association of variables of interest with overall survival and progression-free survival. Results: A total of 304 patients receiving dual immunotherapy (51%) or immunotherapy/vascular endothelial growth factor-tyrosine kinase inhibitor (49%) combinations were eligible for inclusion in this retrospective study. Statin use was a significant prognostic factor for longer overall survival in a univariate analysis (hazard ratio 0.48, 95% confidence interval 0.26–0.87; p = 0.016) and a multivariate analysis (hazard ratio 0.48, 95% confidence interval 0.31–0.74; p < 0.001) and was significantly associated with an overall clinical benefit (83% in statin users vs 71% in non-users; p = 0.045). Otherwise, the use of metformin or proton pump inhibitors did not affect the outcome of these patients. Conclusions: Our study suggests a prognostic impact of statin use in patients receiving first-line immuno-oncology combinations. The mechanism of this interaction warrants further elucidation.