Prognostic impact of proton pump inhibitors for immunotherapy in advanced urothelial carcinoma

Abstract

Objective To evaluate the effects of the concomitant use of proton pump inhibitors (PPIs) and/or antibiotics (Abs) on oncological outcomes in patients with advanced urothelial carcinoma. Patients and methods We retrospectively evaluated 155 patients with advanced urothelial carcinoma who were treated with immune checkpoint inhibitors (ICIs) between August 2015 and April 2021. The concomitant use of PPI or Abs was defined as any PPI or Abs administered within 30 days before ICI initiation and during ICI therapy. The primary outcomes were the effect of PPI and/or Abs use on the objective response rate (ORR) and immune‐related adverse events (irAEs). The secondary outcomes were the effects of PPI and/or Abs use on progression‐free survival (PFS) and overall survival (OS) after ICI therapy analyzed using the inverse probability of treatment weighting‐adjusted Cox regression analysis. Results Of the 155 patients enrolled in the study, 99 (64%) were PPI users and 56 (36%) Abs users. PPI users were associated with a significantly poorer ORR than non‐PPI users (41% vs. 20%, respectively), whereas Abs use was not significantly associated with changes in ORR. The rate of irAEs was not significantly associated with the use of PPIs or Abs. Multivariate inverse probability of treatment weighting‐adjusted Cox regression analysis revealed significantly poorer PFS and OS in PPI users than in non‐PPI users, whereas Abs use was not associated with poorer outcomes. Conclusion The concomitant use of PPI may adversely affect oncological outcomes in patients with locally advanced or metastatic urothelial carcinoma treated with ICI therapy.

Effects of PPIs use on clinical outcomes of urothelial cancer patients receiving immune checkpoint inhibitor therapy

“…We gathered 518 potentially eligible records and assessed their titles and abstracts to see if they were suitable for inclusion. We discovered that six articles ( Hopkins et al, 2020 ; Ruiz-Bañobre et al, 2021 ; Fukuokaya et al, 2022 ; Kunimitsu et al, 2022 ; Okuyama et al, 2022 ; Tomisaki et al, 2022 ) met our criteria for inclusion after carefully reading the full texts of 16 records. The studies on RCC by Peng et al (2022) , Mollica et al (2022) , Kostine et al (2021) only provided the results of univariate analysis, so they were excluded.…”

“…Six studies ( Hopkins et al, 2020 ; Ruiz-Bañobre et al, 2021 ; Fukuokaya et al, 2022 ; Kunimitsu et al, 2022 ; Okuyama et al, 2022 ; Tomisaki et al, 2022 ), involving 1980 participants (759 who received PPIs and 1221 who did not), explored the impact of concomitant PPI usage on adjusted PFS among UC cancers receiving ICI treatment. As shown in Figure 2A , there was no significant heterogeneity among studies (I 2 = 7.4%, p = 0.369), so a fixed-effects model was utilized.…”

“…\The meta-analysis of adjusted OS was performed on six studies ( Hopkins et al, 2020 ; Ruiz-Bañobre et al, 2021 ; Fukuokaya et al, 2022 ; Kunimitsu et al, 2022 ; Okuyama et al, 2022 ; Tomisaki et al, 2022 ) with a total of 1980 participants (759 with PPIs and 1221 without PPIs). Since there was no significant heterogeneity ( Figure 2B , I 2 = 37.4%, p = 0.157), we applied a fixed-effects model.…”

Adapting to the long pandemic

“…Continuing with the advanced urothelial carcinoma theme, the paper by Okuyama et al 6 focused on the specific concerns from immunotherapy trials that concomitant use of proton pump inhibitors for gastro‐oesophageal reflux and/or peptic ulcers or antibiotic use may have negative impacts on the known heterogeneous responses to immunotherapy. They carried out a retrospective, multicentre study of 160 patients with locally advanced or metastatic urothelial cancer treated with checkpoint inhibitors.…”

“…Overall, a total of 52% of their cohorts met eligibility and were associated with significantly poor prognosis, especially driven by lymphovascular invasion and/or positive lymph nodes. Their study presents a useful risk model and several survival metrics from this large cohort.Continuing with the advanced urothelial carcinoma theme, the paper by Okuyama et al6 focused on the specific concerns fromDOI: 10.1002/bco2.139 © 2022 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company BJUI Compass.…”