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.

Chair of Oncology Department of Biomedical Sciences and Human Oncology University of Bari Aldo Moro Bari Italy

Department of Biomedical Sciences Humanitas University Pieve Emanuele Milan Italy

Department of Experimental Diagnostic and Specialty Medicine University of Bologna Bologna Italy

Department of Internal Medicine Hematology Oncology Ochsner Medical Center New Orleans LA USA

Department of Medical and Surgical Sciences and Translational Medicine Faculty of Medicine and Psychology Sapienza University of Rome Rome Italy

Department of Medical Oncology Hospital Ramón y Cajal Madrid Spain

Department of Medical Oncology IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori Meldola Italy

Department of Medical Oncology MD Anderson Cancer Center Madrid Madrid Spain

Department of Oncology 1st Faculty of Medicine Charles University and Thomayer University Hospital Prague Czech Republic

Department of Radiological Oncological and Anatomo Pathological Science Sapienza University of Rome Rome Italy

Department of Surgical Oncological and Oral Sciences Section of Medical Oncology University of Palermo Palermo Italy

Division of Medical Oncology A O U Consorziale Policlinico di Bari Bari Italy

Markey Cancer Center University of Kentucky Lexington KY USA

Medical Oncology Division of Urogenital and Head and Neck Tumours IEO European Institute of Oncology IRCCS Milan Italy

Medical Oncology IRCCS Azienda Ospedaliero Universitaria di Bologna Via Albertoni 15 Bologna Italy

Medical Oncology Unit University Hospital of Parma Parma Italy

Oncology Unit 2 University Hospital of Pisa Pisa Italy

Oncology Unit Macerata Hospital Macerata Italy

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Sex and survival outcomes in patients with renal cell carcinoma receiving first-line immune-based combinations

Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study