Impact of concomitant use of proton pump inhibitors or cardiovascular medication on survival outcomes of patients with metastatic renal cell carcinoma treated with nivolumab

Abstract

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.