Renal cell cancer (RCC) is typically a disease of older adults, who often have comorbidities requiring the use of multiple concomitant medications. Even though the patients with metastatic RCC (mRCC) are often exposed to concomitant medications in parallel with anticancer agents, the impact of such co-medications remains insufficiently explored. The aim of this study was to investigate the impact of the use of proton pump inhibitors (PPIs) and/or cardiovascular medication on the outcomes of patients with mRCC receiving nivolumab. Clinical data of patients with mRCC treated with nivolumab monotherapy were retrospectively analyzed with a focus on the association between progression-free survival (PFS) or overall survival (OS) and the use of common co-medications including PPIs, acetylsalicylic acid, statins, and antihypertensives. In total, 343 patients with mRCC were included. The median PFS and OS were 4.8 (95% CI 3.9–6.0) and 15.5 (95% CI 10.7–19.6) months vs. 9.7 (95% CI 7.6–12.2) and 29.8 (95% CI 23.7–33.1) months (p < 0.001 and p < 0.001) for PPI users and non-users, respectively. In the Cox multivariate analysis, the use of PPIs remained a significant factor predicting both inferior PFS (HR = 1.870 [95% CI 1.440–2.428], p < 0.001) and OS (HR = 1.674 [95% CI 1.235–2.270], p = 0.001).). We did not find any impact of the basic classes of antihypertensive drugs, statins, or acetylsalicylic acid on the survival outcomes. Present study results demonstrate the negative impact of concomitant PPI use on PFS and OS, whereas neither statins nor antihypertensive medications had a significant impact on survival outcomes in patients with mRCC receiving nivolumab monotherapy.

Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 76 Pilsen 304 60 Czech Republic

Department of Comprehensive Cancer Care Faculty of Medicine Masaryk University Kamenice 5 Brno 625 00 Czech Republic

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Zluty kopec 7 Brno 656 53 Czech Republic

Department of Oncology 1st Faculty of Medicine Charles University and General University Hospital U Nemocnice 499 2 Prague 128 08 Czech Republic

Department of Oncology 1st Faculty of Medicine Charles University and Thomayer University Hospital Videnska 800 Prague 140 59 Czech Republic

Department of Oncology 2nd Faculty of Medicine Charles University and Motol University Hospital 5 Úvalu 84 Prague 150 06 Czech Republic

Department of Oncology and Radiotherapeutics Faculty of Medicine and University Hospital in Pilsen Charles University Czech Republic Alej Svobody 80 Pilsen 304 60 Czech Republic

Department of Oncology and Radiotherapeutics Faculty of Medicine in Pilsen Charles University Alej Svobody 80 Pilsen 304 60 Czech Republic

Department of Oncology Palacký University Medical School and Teaching Hospital 1 P Pavlova 6 Olomouc 775 20 Czech Republic

Department of Oncology University Hospital in Hradec Králové Sokolská 581 Hradec Králové 50005 Czech Republic

Department of Urology Faculty of Medicine and University Hospital in Pilsen Charles University Czech Republic Edvarda Beneše 1128 13 Pilsen 301 00 Czech Republic

Institute of Biostatistics and Analyses Ltd Poštovská 68 3 Brno 602 00 Czech Republic

University Hospital Pilsen Pilsen Czech Republic

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