Concomitant Proton Pump Inhibitors and Outcome of Patients Treated with Nivolumab Alone or Plus Ipilimumab for Advanced Renal Cell Carcinoma

Target Oncol. 2022 Jan;17(1):61-68. doi: 10.1007/s11523-021-00861-y. Epub 2021 Dec 11.

Abstract

Background: Immune checkpoint inhibitors (ICIs) represent the standard of care as first- or second-line treatment in patients with renal cell carcinoma (RCC). Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide and are known to affect gut microbiota, which is gaining interest in its association with outcomes for patients on ICIs.

Objective: The aim of this study was to evaluate the impact of PPIs on outcomes in RCC patients receiving immunotherapy.

Patients and methods: We retrospectively collected data from patients with metastatic RCC who received the combination of ipilimumab and nivolumab for first-line treatment (Cohort 1) or single-agent nivolumab for second-line or third-line treatment (Cohort 2) from five international centers with expertise in the treatment of RCC. Data about clinicopathological characteristics, PPI use, and outcome on ICIs were collected. Endpoints of the study were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results: Two hundred and eighteen patients (71% male, median age 61 years) were included in the analysis, 62 in Cohort 1 (including 25 patients receiving PPIs) and 156 in Cohort 2 (including 88 patients receiving PPIs), and were followed up for a median of 42 months. In Cohort 1, no difference was observed in ORR (48% vs 57%; p = 0.203), PFS (12.2 vs 8.5 months; p = 0.928), or OS (not reached [NR] vs 27.3 months; p = 0.84). In Cohort 2, no difference was observed in ORR (32% vs 28%; p = 0.538), PFS (6.7 vs 9.0 months; p = 0.799), or OS (16.0 vs 26.0 months; p = 0.324).

Conclusions: In patients with RCC, concomitant PPI use did not seem to affect survival outcomes on ICIs, either as combination therapy or monotherapy.

MeSH terms

  • Carcinoma, Renal Cell* / drug therapy
  • Female
  • Humans
  • Ipilimumab / pharmacology
  • Ipilimumab / therapeutic use
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / pathology
  • Male
  • Middle Aged
  • Nivolumab / adverse effects
  • Proton Pump Inhibitors / pharmacology
  • Proton Pump Inhibitors / therapeutic use
  • Retrospective Studies

Substances

  • Ipilimumab
  • Proton Pump Inhibitors
  • Nivolumab