Association of gastric acid suppression with efficacy of immune checkpoint inhibitors (ICIs) in advanced cancer patients

Abstract

Abstract Background Recent studies have shown that proton pump inhibitor (PPI) negatively impacts on the clinical benefit from ICIs. Gut microbiome modulated by PPI may contribute to decreased efficacy. It has been also reported that H2 blocker (H2B) or gastrectomy affected gut microbiome. We assessed in this study the association of GAS including PPI, H2B and gastrectomy with clinical outcome from ICI. Methods We retrospectively investigated advanced cancers pts treated with ICIs as the 1st- to the 3rd-line treatment at our institution between July 2014 and September 2018. GAS was defined as using PPI or H2B within 30 days before start of ICI, or having past history of gastrectomy. Response to ICIs was assessed by RECIST v1.1. Performance status (PS), body mass index, antibiotics, steroid, LDH level, albumin level, CPR and neutrophil-lymphocyte ratio (NLR) were compared between the GAS and non-GAS arms. Associations of nominal variables with the response were evaluated. Results Total of 115 pts (lung 69.9%, skin 11.3%, head and neck 7.8%, renal cell 6.9%, stomach 4.2%, and urothelium 2.5%) were evaluated. The types of ICIs were nivolumab of 72.2%, pembrolizumab of 22.6%, and atezolizumab of 5.2%. Sixty of 115 pts recieved GAS (PPI 83.3%, H2B 11.6%, and gastorectomy 5%) before start of ICI. Patients’ characteristics between the GAS and non-GAS arms was almost well balanced. However, pts with lower PS (>2) or high NLR were more frequently observed in the GAS arm (20% vs. 0%, 40% vs. 16%, respectively). The response rate (RR) was almost significantly lower in the GAS arm than the non-GAS arm (12% vs. 25%, P = 0.055). GAS did not remain statistically significant in a multivariate analysis (P = 0.091), while LDH was significant in both uni- and multivariate analyses. Conclusion Pts with GAS and pts without GAS have different patients’ background such as PS and NLR, and the RR in pts with GAS was numerically lower compared to that without GAS in advanced cancer treated with ICI.