Efficacy of PD-1/PD-L1 therapy: Do proton pump inhibitors affect the outcome?

Abstract

208 Background: Recent studies have shown that manipulating the gut microbiome modulates the efficacy of anti-PD1/PD-L1 directed therapy leading to increase in the activity of CD8+ T-cells. Proton Pump inhibitors (PPIs) affect the gut microbiome. The objective of this study was to investigate the effects of PPIs use on agents that target the PD-1/PD-L1 pathway in patients treated with these agents. Methods: We looked at the outcomes of 158 patients aged 18 years or older, treated at the University of Oklahoma Health Sciences Center between 2014 and 2016. The primary aim of this study was to investigate whether survival of patients treated with agents that target PD-1/PD-L1 pathway was affected by PPI use. The secondary objective was to identify if there is any difference in the immune related side effect profile between PPI users and non-users. The overall survival (OS) and progression free survival (PFS) were compared between PPI users and nonusers using the log-rank tests. Survival curves were generated using the Kaplan-Meyer method. The proportions of Grade 3 or 4 colitis or pneumonitis were compared between PPI users and nonusers using the Fisher’s exact test. SAS 9.4 was used for the statistical analysis and a 0.05 significance level was used. Results: The majority of patients were females (57%). The median age was 63 years. Lung cancer was the most common diagnosis (20%) followed by melanoma (20%) and ovarian cancer (12%). Nivolumab was the most commonly used agent (47%) followed by Pembrolizumab (22%), other investigational agents (22%) and Atezolizumab (7%). The median follow-up time from the date of first PPI dose was 7 months. There was no statistically significant difference in OS or PFS between PPI users and nonusers (p = 0.77). There were no significant differences in proportions of Grade 3 or 4 colitis between PPI users and nonusers (5% vs. 5.26%, p > .99). Similarly, there were no significant differences in proportions of Grade 3 or 4 pneumonitis between PPI users and nonusers (6.25% vs. 1.75%, p = 0.40). Conclusions: Use of PPI does not affect the outcome of patients receiving agents that target PD1/PD-L1 pathway. The incidence of important immune related side effects was similar between PPI users and non-users.