TY - JOUR
T1 - Impact of Proton Pump Inhibitor Use on the Effectiveness of Immune Checkpoint Inhibitors in Advanced Cancer Patients
AU - Peng, Kangning
AU - Chen, Ken
AU - Teply, Benjamin A.
AU - Yee, Gary C.
AU - Farazi, Paraskevi A.
AU - Lyden, Elizabeth R.
N1 - Funding Information:
We would like to sincerely thank Dr Lorena Baccaglini for support on research proposal preparation and IRB application, and Dr Donald G. Klepser for support on IRB application. The authors received no financial support for the research, authorship, and/or publication of this article.
Publisher Copyright:
© The Author(s) 2021.
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - advanced cancer
KW - drug-drug interactions
KW - gut microbiome
KW - programmed cell death-1 inhibitors
KW - proton pump inhibitors
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U2 - 10.1177/10600280211033938
DO - 10.1177/10600280211033938
M3 - Article
C2 - 34282636
AN - SCOPUS:85110948687
VL - 56
SP - 377
EP - 386
JO - Annals of Pharmacotherapy
JF - Annals of Pharmacotherapy
SN - 1060-0280
IS - 4
ER -