TY - JOUR
T1 - Association of proton pump inhibitor use with survival outcomes in cancer patients treated with immune checkpoint inhibitors
T2 - a systematic review and meta-analysis
AU - Chen, Baoqing
AU - Yang, Chen
AU - Dragomir, Mihnea P.
AU - Chi, Dongmei
AU - Chen, Wenyan
AU - Horst, David
AU - Calin, George A.
AU - Li, Qiaoqiao
N1 - Funding Information:
The authors specially thank Dr. Spakowicz (Division of Medical Oncology, The Ohio State University Medical Center), Dr. Kulkarni (University of Minnesota, Minneapolis, MN, USA), and Dr. Nguyen (Department of Medical Oncology, Kyoto University) and their teams for generously sharing with us the data, which are not available in the online version of the publications or abstracts. Editorial support was provided by Bryan Tutt, Scientific Editor, Research Medical Library, MD Anderson Cancer Center. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Natural Science Foundation of China (No. 81902462 to B.Q.C.), Berlin Institute of Health (to M.P.D.), DKTK Berlin Young Investigator Grant 2022 (to M.P.D.), Berliner Krebsgesellschaft (DRFF202204 to M.P.D.), National Cancer Institute at the U.S. National Institutes of Health (1R01CA182905-01 and 1R01CA222007-01A1 to G.A.C.), National Institute of General Medical Sciences at the U.S. National Institutes of Health (1R01GM122775-01 to G.A.C.), and U.S. Department of Defense (W81XWH2110030 to G.A.C.).
Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Natural Science Foundation of China (No. 81902462 to B.Q.C.), Berlin Institute of Health (to M.P.D.), DKTK Berlin Young Investigator Grant 2022 (to M.P.D.), Berliner Krebsgesellschaft (DRFF202204 to M.P.D.), National Cancer Institute at the U.S. National Institutes of Health (1R01CA182905-01 and 1R01CA222007-01A1 to G.A.C.), National Institute of General Medical Sciences at the U.S. National Institutes of Health (1R01GM122775-01 to G.A.C.), and U.S. Department of Defense (W81XWH2110030 to G.A.C.).
Funding Information:
The authors specially thank Dr. Spakowicz (Division of Medical Oncology, The Ohio State University Medical Center), Dr. Kulkarni (University of Minnesota, Minneapolis, MN, USA), and Dr. Nguyen (Department of Medical Oncology, Kyoto University) and their teams for generously sharing with us the data, which are not available in the online version of the publications or abstracts. Editorial support was provided by Bryan Tutt, Scientific Editor, Research Medical Library, MD Anderson Cancer Center.
Publisher Copyright:
© The Author(s), 2022.
PY - 2022
Y1 - 2022
N2 - Background: Proton pump inhibitors (PPIs) have been shown to regulate the gut microbiome and affect the response to immune checkpoint inhibitors (ICIs). Contradictory results on survival have been observed in patients concomitantly treated with ICIs and PPIs. We performed a systematic review and meta-analysis to determine the association between PPI use and survival outcomes in ICI-treated cancer patients. Methods: EMBASE, MEDLINE/PubMed, Cochrane Library databases, and major oncology conference proceedings were searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI-treated and PPI-free groups of ICI-treated cancer patients were included. Data regarding study and patient characteristics, ICI and PPI treatments, and survival outcomes were extracted. Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using random effects models. Subgroup meta-analyses and meta-regressions were performed to explore possible factors of heterogeneity among the studies. Results: A total of 33 studies were included, comprising 7383 ICI- and PPI-treated patients and 8574 ICI-treated and PPI-free patients. The pooled HR was 1.31 (95% CI, 1.19–1.44; p < 0.001) for OS and 1.30 (95% CI, 1.17–1.46; p < 0.001) for PFS, indicating a significant negative association between PPI use and survival in ICI-treated patients. Subgroup meta-analyses by factors including cancer type, ICI type, and time window of PPI use revealed that ICI and PPI use impacted survival in patients with non-small cell lung or urothelial cancer, patients treated with anti-PD-1/PD-L1 antibodies, and patients receiving PPI as baseline treatment or 60 days before ICI treatment initiation. Conclusions: PPI use in patients treated with ICIs was associated with shorter OS and PFS, especially in several specific subgroups of cancer patients. PPIs should be strictly controlled and appear to not impact survival if given temporarily after ICI initiation. These observations could provide the basis for clinical guidelines for concomitant PPI and ICI use.
AB - Background: Proton pump inhibitors (PPIs) have been shown to regulate the gut microbiome and affect the response to immune checkpoint inhibitors (ICIs). Contradictory results on survival have been observed in patients concomitantly treated with ICIs and PPIs. We performed a systematic review and meta-analysis to determine the association between PPI use and survival outcomes in ICI-treated cancer patients. Methods: EMBASE, MEDLINE/PubMed, Cochrane Library databases, and major oncology conference proceedings were searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI-treated and PPI-free groups of ICI-treated cancer patients were included. Data regarding study and patient characteristics, ICI and PPI treatments, and survival outcomes were extracted. Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using random effects models. Subgroup meta-analyses and meta-regressions were performed to explore possible factors of heterogeneity among the studies. Results: A total of 33 studies were included, comprising 7383 ICI- and PPI-treated patients and 8574 ICI-treated and PPI-free patients. The pooled HR was 1.31 (95% CI, 1.19–1.44; p < 0.001) for OS and 1.30 (95% CI, 1.17–1.46; p < 0.001) for PFS, indicating a significant negative association between PPI use and survival in ICI-treated patients. Subgroup meta-analyses by factors including cancer type, ICI type, and time window of PPI use revealed that ICI and PPI use impacted survival in patients with non-small cell lung or urothelial cancer, patients treated with anti-PD-1/PD-L1 antibodies, and patients receiving PPI as baseline treatment or 60 days before ICI treatment initiation. Conclusions: PPI use in patients treated with ICIs was associated with shorter OS and PFS, especially in several specific subgroups of cancer patients. PPIs should be strictly controlled and appear to not impact survival if given temporarily after ICI initiation. These observations could provide the basis for clinical guidelines for concomitant PPI and ICI use.
KW - cancer
KW - immune checkpoint inhibitors
KW - meta-analysis
KW - proton pump inhibitor
KW - survival
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U2 - 10.1177/17588359221111703
DO - 10.1177/17588359221111703
M3 - Article
C2 - 35860836
AN - SCOPUS:85134678611
SN - 1758-8340
VL - 14
JO - Therapeutic Advances in Medical Oncology
JF - Therapeutic Advances in Medical Oncology
ER -