Concomitant Proton Pump Inhibitors and Immune Checkpoint Inhibitors Increase Nephritis Frequency

Abstract Background: The emergence of immune checkpoint inhibitors has greatly changed the treatment outcome of advanced malignant tumors. The basic medication for patients with advanced solid tumors may affect the efficacy of immunotherapy. The use of proton pump inhibitors may change the acidic environment and inhibit intestinal flora, thereby affecting the efficacy of immunotherapy. To clarify the correlation between PPI administration and the prognosis of solid cancer patients treated with ICI, we conducted a meta-analysis.Method: Before February 12th, 2021, PubMed, Cochrane Library, Web of Science and EMBASE databases were used to search for eligible documents. The association of PPI administration with overall survival (OS) and progression-free survival (PFS), hazard ratio (HR) and 95% confidence interval (CI) were determined.Results: This study included 10 studies, a total of 4072 patients with solid cancer who received ICI treatment. Overall, the PPI administered with OS (HR=1.31 (1.11-1.52), P = 0.001) deteriorate significantly associated. In the subgroup analysis based on cancer type, PPI administration was associated with worsening of PFS in NSCLC, and better results of PFS in melanoma patients. In addition, between 30 days before the occurrence of ICI and 30 days after the occurrence of ICI, PPI administration may reduce the efficacy of ICI. Conclusion: Patients with solid cancer receiving ICI should use PPI with caution. However, only poor statistical results are observed on the OS, and further verification is still essential. This study was registered in PROSPERO with registration number CRD42021243707.

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Impact of Antibiotics and Proton Pump Inhibitors on Efficacy and Tolerance of Anti-PD-1 Immune Checkpoint Inhibitors

Frontiers in Immunology ◽

10.3389/fimmu.2021.716317 ◽

2021 ◽

Vol 12 ◽

Author(s):

Quentin Giordan ◽

Julia Salleron ◽

Catherine Vallance ◽

Clothilde Moriana ◽

Christelle Clement-Duchene

Keyword(s):

Adverse Events ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Small Cell Lung Carcinoma ◽

Progression Free Survival ◽

Cell Lung Carcinoma ◽

The Impact

BackgroundThe use of antibiotics (ATB) and proton-pump inhibitors (PPI) alters the composition and diversity of the gut microbiota, which can influence the immune system, consequently interfering with response to anti-PD1 immune checkpoint inhibitors (ICI). We assessed the impact of ATB and/or PPI use on the efficacy and safety of ICI.MethodsTwo hundred twelve patients treated with anti-PD1 ICI for non-small cell lung carcinoma, melanoma, upper airway & digestive tract carcinoma or renal cell carcinoma were retrospectively included. Patients having received ATB within 60 days before ICI initiation were included in the ATB+ group. Patients having received PPI within 30 days before ICI initiation were included in the PPI+ group. Four groups were thus considered: ATB-/PPI-, ATB+/PPI-, ATB-/PPI+, ATB+/PPI+. Response rate was assessed by RECIST v1.1. Overall survival (OS), progression-free survival (PFS) and adverse events, recorded using Common Terminology Criteria for Adverse Events Version 5, were compared using inverse probability of treatment weighting to account for selection bias.ResultsPFS at 6 months was 56.7 %, 95%CI (49.6%; 63.2%) and 47.2 %, 95%CI (39.8%;54.1%) at 12 months. OS was 81.6%, 95%CI (75.6%; 86.2%) at 6 months, and 69.4%, 95%CI (61.9%;75.7%) at 12 months. Compared to ATB-/PPI- group, PFS was lower for the ATB+/PPI- group [Hazard ratio (HR) 1.90, 95%CI (1.41;2.57)] and the ATB-/PPI+ group [HR 1.51, 95%CI (1.11;2.05)], and lowest in the ATB+/PPI+ group [HR 3.65, 95%CI (2.75;4.84)]. For OS, the use of ATB alone or PPI alone or in combination was a risk factor for death, with each increasing HR values by a similar magnitude, and the combination of ATB and PPI did not increase risk further. AEs were observed in 78 cases (36.8%) with no significant impact of ATB or PPI use.ConclusionsThis study reveals that ATB and/or PPI use can alter response to anti-PD1 ICI, and the prognosis of cancer patients. The microbiota mechanisms involved in the response to ICI should be investigated to optimize patient management.

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

Annals of Pharmacotherapy ◽

10.1177/10600280211033938 ◽

2021 ◽

pp. 106002802110339

Author(s):

Kangning Peng ◽

Ken Chen ◽

Benjamin A. Teply ◽

Gary C. Yee ◽

Paraskevi A. Farazi ◽

...

Keyword(s):

Cell Carcinoma ◽

Cancer Patients ◽

Advanced Cancer ◽

Proton Pump ◽

Gut Microbiome ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Critical Role ◽

The Impact

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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