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Efficacy and safety of concomitant proton pump inhibitor and nivolumab in renal cell carcinoma: results of the GETUG-AFU 26 NIVOREN multicenter phase II study

      Highlights

      • The GETUG-AFU 26 NIVOREN trial enrolled 729 mRCC patients of whom 27.7% were PPI users
      • PPI use did not correlate with PFS or OS (HR = 0.89, 95% CI 0.74-1.08 and HR = 1.24; 95% CI, 0.98-1.58, respectively).
      • Nivolumab-related adverse events of any grade occurred similarly among PPI users and non-users (61.2% vs 62%).
      • Grade 3-5 nivolumab-related adverse events were more common among PPI users (25.5% vs 15.3%).

      Abstract

      Microabstract

      As proton pump inhibitors (PPI) were shown to impact the effectiveness of immune checkpoint inhibitors (ICI) in lung and bladder cancers, we sought to evaluate the effect of PPIs on the outcomes patients with metastatic renal cell carcinoma (mRCC) treated with ICI.

      Introduction

      Proton pump inhibitors (PPI) may influence the gut microbiome and thus impact the effectiveness of immune checkpoint inhibitors (ICI). The effect of PPIs on the outcomes of ICI has not been fully explored and investigated in metastatic renal cell carcinoma (mRCC).

      Methods

      This retrospective analysis used prospectively collected data from the GETUG-AFU 26 NIVOREN (NCT03013335) phase II study which enrolled 729 mRCC patients of whom 720 were treated with nivolumab. The main objective of this analysis was to evaluate the impact of PPI on the efficacy and safety outcomes of mRCC patients. PPI use was defined as PPI administration on the day of ICI initiation.

      Results

      Of the 707 patients with mRCC analyzed in this study, 196 (27.7%) were PPI users. The majority of PPI users were males (80.6%), had an ECOG performance status of 0-1 (78.9%) and a nephrectomy (82.1%). Almost two-thirds of the patients had a favorable and intermediate IMDC risk category and 52% received nivolumab in the third line and beyond. PPI use did not correlate with PFS or OS (HR = 0.89, 95% CI 0.74-1.08 and HR = 1.24; 95% CI, 0.98-1.58, respectively). Grade 3-5 nivolumab-related adverse events were more common among PPI users (25.5% vs 15.3%).

      Conclusions

      This real-world study suggests that PPI use in patients with mRCC does not impact the efficacy outcomes but may influence the safety of nivolumab which warrants further investigations.

      Keywords

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