Document Type

Capstone Experience

Graduation Date

5-2021

Degree Name

Master of Public Health

Department

Epidemiology

First Committee Member

Paraskevi A. Farazi, PhD

Second Committee Member

Gary C. Yee, PharmD

Third Committee Member

Elizabeth Lyden, MS

Abstract

Background: Gut microbiome plays a critical role in modulating therapeutic effect of immune checkpoint inhibitors (ICIs). Proton pump inhibitors (PPIs) may affect the gut microbiome by altering gut pH.

Objective: To evaluate if concurrent use of PPI 0-30 days before or after initiation of ICIs (nivolumab or pembrolizumab) is associated with poorer overall survival (OS) and progression-free survival (PFS) for patients with stage IV non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, transitional cell carcinoma or head and neck squamous cell carcinoma compared with no PPI use.

Methods: This was a single-center retrospective cohort study of advanced cancer patients with concomitant PPI and nivolumab or pembrolizumab use compared with nivolumab or pembrolizumab use alone with OS and PFS as outcomes.

Results: A total of 233 patients were included in our study. Concomitant use of PPI did not have a significant impact on OS (Hazard ratio (HR) 1.22, 95% confidence interval (CI) 0.80 to 1.86) or PFS (HR 1.05, 95%CI 0.76 to 1.45) in patients with ICI use. The effect estimates were robust after adjusting for covariates in multivariate analysis and in patients with NSCLC.

Conclusion and Relevance: The impact of PPI on effectiveness of nivolumab or pembrolizumab use was limited. Certain predictors of survival outcomes related to PPI use in patients receiving immunotherapy, such as duration of treatment and time of PPI exposure, and autoimmune disorders, should be explored in the future to better carve out the impact of PPI on effectiveness of ICI use.

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