LAUSR

Abstract Background Solid tumors are characterized by a highly acidic microenvironment that might hamper anti-cancer immunity. Several studies have shown that proton pump inhibitors (PPIs) can neutralize the pH of the tumor microenvironment and indirectly affect the function of cytotoxic T lymphocytes, suggesting a possible impact on clinical outcomes of immunotherapies. The aim of this analysis to explore the relationship between the use of PPIs and the efficacy of nivolumab monotherapy in 4 different types of cancer: malignant melanoma (MM), renal cell carcinoma (RCC), gastric cancer (GC), and head and neck cancer (HN). Methods A retrospective chart review was performed on 95 consecutive patients treated with nivolumab monotherapy between October 2014 and December 2018 at our hospital. Co-medication of PPIs was defined if the patient was prescribed any types of PPIs for more than 2 weeks during the administration of nivolumab. Response rates (RR), progression-free survival (PFS) and overall survival (OS) were compared between PPI users and non-users. Results The majority of patients were males (65.3%). The median age was 68 years. MM was the most common diagnosis (47.4%) followed by HN (24.2%) and GC (17.8%). PPIs were prescribed in 42% of the cases. There was no statistically significant difference in RR, OS or PFS between PPI users and non-users in GC and HN. However, co-medication of PPIs was associated with lower RR in MM, but higher RR in RCC. Although these results did not translate into significant changes in the PFS or OS, differences were observed in the Kaplan-Meyer curves of these two types of cancer. Conclusion Our analysis shows that PPIs could have different impact on the benefit of nivolumab monotherapy. These results suggest that unnecessary prescription of PPIs should be avoided in patients who are receiving PD1-based immunotherapy for the treatment of MM, and the effect of PPIs should be considered in interpreting the results from clinical trials.