Effects of concomitant proton pump inhibitor use on immune checkpoint inhibitor efficacy among patients with advanced cancer

Qin, Bao‐Dong; Jiao, Xiao‐Dong; Zhou, Xin-Cheng; Shi, Bin; Wang, Jian; Liu, Ke; Wu, Ying; Ling, Yan

doi:10.1080/2162402x.2021.1929727

Cited by 37 publications

(34 citation statements)

References 44 publications

(83 reference statements)

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“…Therefore, in this study, we performed an up-to-date metaanalysis to clarify the correlation between PPI use and ICI efficacy in advanced solid cancers. During the preparation of our manuscript, it is worth mentioning that three similar studies have been published so far (36)(37)(38). Compared with them, on the one hand, our present work is an up-to-date analysis including more studies (n = 17 vs.…”

Section: Publication Bias and Sensitivity Analysismentioning

confidence: 89%

“…On the contrary, an updated investigation by Qin et al. in 2021 demonstrated a significant negative correlation of PPI use with OS and PFS in advanced cancer patients treated with ICIs ( 38 ). Despite the lack of supporting mechanism investigations, Qin et al.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, compared with antibiotics, the impact of PPIs on the gut microbiome is relatively limited, and there is a lack of sequencing studies to identify dominant bacteria affected by PPIs in ICI nonresponders. On the contrary, an updated investigation by Qin et al in 2021 demonstrated a significant negative correlation of PPI use with OS and PFS in advanced cancer patients treated with ICIs (38). Despite the lack of supporting mechanism investigations, Qin et al hypothesized that PPIs may decrease ICI efficacy by altering the abundance of some bacteria via increasing pH levels.…”

Section: Publication Bias and Sensitivity Analysismentioning

confidence: 99%

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An Up-To-Date Investigation Into the Correlation Between Proton Pump Inhibitor Use and the Clinical Efficacy of Immune Checkpoint Inhibitors in Advanced Solid Cancers: A Systematic Review and Meta-Analysis

et al. 2022

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BackgroundAlthough immune checkpoint inhibitors (ICIs) have revolutionized the current anticancer therapies, a considerable proportion of patients are found to hardly benefit from these drugs. Accumulating studies have demonstrated that concomitant proton pump inhibitor (PPI) use may affect the clinical efficacy of ICIs; however, their results are inconsistent. In this study, based on updated evidence, we aimed to perform a meta-analysis to clarify the prognostic significance of PPI use in advanced solid cancer patients receiving ICI therapy.MethodsEligible literature was searched using PubMed, Cochrane Library, Web of Science, EMBASE, and other network resources before July 2021. Clinical outcome was evaluated using overall survival (OS) and progression-free survival (PFS). The correlation of PPI use with OS or PFS was determined based on hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsA total of 17 studies enrolling 9,978 ICI-treated cancer patients were included in our meta-analysis. The global analysis demonstrated that PPI use was significantly correlated with worse OS [HR = 1.29 (1.10–1.50)] instead of PFS [HR = 1.19 (0.98–1.44)] in solid cancer patients receiving ICI therapy. In a subgroup analysis, the negative correlation of PPI use with ICI efficacy was significant in patients with non-small cell lung cancer [PFS, HR = 1.27 (1.10–1.47)] and urothelial carcinoma [OS, HR = 1.55 (1.31–1.84), PFS, HR = 1.52 (1.13–2.06)] and mixed cohorts containing multiple cancer types [OS, HR = 1.40 (1.16–1.69)], while an opposite result was observed in the PFS of patients with melanoma [HR = 0.48 (0.25–0.90)]. Moreover, the unfavorable prognostic impact of PPI use was also significant in patients over 65 years old [OS, HR = 1.28 (1.05–1.55), PFS, HR = 1.32 (1.12–1.56)] or those receiving anti-PD-1 [OS, HR = 1.37 (1.04–1.79)] or anti-PD-L1 therapies (OS, HR = 1.49 (1.30–1.69), PFS, HR = 1.34 (1.20–1.50). Finally, PPI use was significantly correlated with a worse prognosis in patients receiving PPIs 30 days before and/or after ICI initiation (OS, HR = 1.38 (1.18–1.62), PFS, HR = 1.23 (1.06–1.43)).ConclusionAlthough our global analysis revealed PPI use was not correlated with the PFS of ICI-treated patients, considering the results of our subgroup analysis, PPIs should be still cautiously used shortly before or during ICI therapy. Furthermore, more clinical validations and related mechanism investigations are of great necessity to clarify the clinical correlation of PPI use with ICI efficacy.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/], PROSPERO [No. CRD42021243707].

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Section: Publication Bias and Sensitivity Analysismentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Publication Bias and Sensitivity Analysismentioning

confidence: 99%

See 1 more Smart Citation

An Up-To-Date Investigation Into the Correlation Between Proton Pump Inhibitor Use and the Clinical Efficacy of Immune Checkpoint Inhibitors in Advanced Solid Cancers: A Systematic Review and Meta-Analysis

et al. 2022

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“…Recently, a meta-analysis of seven studies (3647 cancer patients) was reported. The authors concluded that PPIs’ use had a detrimental effect on the efficacy of ICI: PPIs’ use increased the risk of death by 39% and the risk of progression by 28% [ 63 ].…”

Section: Ppis and Oncologic Treatment Efficacymentioning

confidence: 99%

Long-Term Use of Proton Pump Inhibitors in Cancer Patients: An Opinion Paper

Raoul

Edeline

Simmet

et al. 2022

Cancers

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Multikinase inhibitors (MKIs), and particularly tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (CPIs), are currently some of the major breakthroughs in cancer treatment. Proton pump inhibitors (PPIs) revolutionised the treatment of acid-related diseases, but are frequently overused for epigastric pain or heartburn. However, long-term acid suppression from using PPIs may lead to safety concerns, and could have a greater impact in cancer patients undergoing therapy, like bone fractures, renal toxicities, enteric infections, and micronutrient deficiencies (iron and magnesium). Moreover, acid suppression may also affect the pharmacokinetics of drugs (at least during acid suppression) and decrease the absorption of many molecularly-targeted anticancer therapies, which are mostly weak bases with pH-dependent absorption. This type of drug-drug interaction may have detrimental effects on efficacy, with major clinical impacts described for some orally administrated targeted therapies (erlotinib, gefitinib, pazopanib, palbociclib), and conflicting results with many others, including capecitabine. Furthermore, the long-term use of PPIs results in severe alterations to the gut microbiome and recent retrospective analyses have shown that the benefit of using CPIs was suppressed in patients treated with PPIs. These very expensive drugs are of great importance because of their efficacy. As the use of PPIs is not essential, we must apply the precautionary principle. All these data should encourage medical oncologists to refrain from prescribing PPIs, explaining to patients the risks of interaction in order to prevent inappropriate prescription by another physician.

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“…Finally, other medications (e.g. antibiotics [82], proton‐pump inhibitors [83]) or dietary choices (e.g. high‐fibre intake [84]) may impact ICI efficacy (negatively or positively, respectively) via influencing our gut microbiome – the composition and diversity of resident microbiota living in our gastrointestinal tract.…”

Section: Phenotypic and External Featuresmentioning

confidence: 99%

‘Know thyself’ – host factors influencing cancer response to immune checkpoint inhibitors

Gunjur

Manrique-Rincón

Klein

et al. 2022

The Journal of Pathology

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Immune checkpoint inhibitors (ICIs) have revolutionised oncology and are now standard-of-care for the treatment of a wide variety of solid neoplasms. However, tumour responses remain unpredictable, experienced by only a minority of ICI recipients across malignancy types. Therefore, there is an urgent need for better predictive biomarkers to identify a priori the patients most likely to benefit from these therapies. Despite considerable efforts, only three such biomarkers are FDA-approved for clinical use, and all rely on the availability of tumour tissue for immunohistochemical staining or genomic assays. There is emerging evidence that host factorsfor example, genetic, metabolic, and immune factors, as well as the composition of one's gut microbiotainfluence the response of a patient's cancer to ICIs. Tantalisingly, some of these factors are modifiable, paving the way for co-therapies that may enhance the therapeutic index of these treatments. Herein, we review key host factors that are of potential biomarker value for response to ICI therapy, with a particular focus on the proposed mechanisms for these influences.

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Effects of concomitant proton pump inhibitor use on immune checkpoint inhibitor efficacy among patients with advanced cancer

Cited by 37 publications

References 44 publications

An Up-To-Date Investigation Into the Correlation Between Proton Pump Inhibitor Use and the Clinical Efficacy of Immune Checkpoint Inhibitors in Advanced Solid Cancers: A Systematic Review and Meta-Analysis

An Up-To-Date Investigation Into the Correlation Between Proton Pump Inhibitor Use and the Clinical Efficacy of Immune Checkpoint Inhibitors in Advanced Solid Cancers: A Systematic Review and Meta-Analysis

Long-Term Use of Proton Pump Inhibitors in Cancer Patients: An Opinion Paper

‘Know thyself’ – host factors influencing cancer response to immune checkpoint inhibitors

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