Impact of Proton Pump Inhibitor Use on the Effectiveness of Immune Checkpoint Inhibitors in Advanced Cancer Patients

Jul 20, 2021The Annals of pharmacotherapy

Proton Pump Inhibitors May Reduce the Effectiveness of Immune Therapy in Advanced Cancer Patients

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Abstract

A total of 233 patients were included in the analysis of immune checkpoint inhibitors and proton pump inhibitors.

Concomitant use of proton pump inhibitors was not significantly associated with overall survival in patients receiving immune checkpoint inhibitors.
The hazard ratio for overall survival with proton pump inhibitors was 1.22, indicating no significant impact.
Similarly, no significant association was found between proton pump inhibitor use and progression-free survival, with a hazard ratio of 1.05.
The findings remained consistent after adjusting for various factors in multivariate analysis.
Further investigation is suggested to explore specific predictors related to proton pump inhibitor use and survival outcomes.

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BACKGROUND: The gut microbiome plays a critical role in modulating the therapeutic effect of immune checkpoint inhibitors (ICIs). Proton pump inhibitors (PPIs) are commonly used in cancer patients and may affect the gut microbiome by altering gut pH.

OBJECTIVE: To evaluate if concurrent use of PPI is associated with overall survival (OS) and progression-free survival (PFS) in patients with stage IV non-small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma, transitional cell carcinoma, or head and neck squamous cell carcinoma.

METHODS: This was a single-center retrospective cohort study of advanced cancer adult patients who received nivolumab or pembrolizumab between September 1, 2014, and August 31, 2019. Concomitant PPI exposure was defined as PPI use 0 to 30 days before or after initiation of ICIs. Treatment outcome was OS and PFS.

RESULTS: A total of 233 patients were included in our study. Concomitant PPI use was not significantly associated with OS (hazard ratio [HR] = 1.22; 95% CI = 0.80-1.86) or PFS (HR = 1.05; 95% CI = 0.76-1.45) 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: Concomitant PPI use was not associated with the effectiveness of nivolumab or pembrolizumab. Certain predictors of survival outcomes related to PPI use in patients receiving immunotherapy, such as the time window and indication of PPI exposure and autoimmune disorders, should be explored in the future to better carve out the impact of PPI on the effectiveness of ICI use.

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Impact of Proton Pump Inhibitor Use on the Effectiveness of Immune Checkpoint Inhibitors in Advanced Cancer Patients

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