The association between proton pump inhibitors use and clinical outcome of patients receiving immune checkpoint inhibitors therapy

Li, Manyu; Zeng, Chaofan; Yao, Jiannan; Ge, Yang; An, Guangyu

doi:10.1016/j.intimp.2020.106972

Cited by 28 publications

(41 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 90%

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

View full text Add to dashboard Cite

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].

show abstract

Section: Publication Bias and Sensitivity Analysismentioning

confidence: 90%

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

View full text Add to dashboard Cite

show abstract

“…PPI action is not only limit ed to the intestinal flora, but also that the tumor has been resistant to immunotherapy regenera te sensitive (34). During the preparation of our manuscript, we noticed that two meta-analyses w ere conducted last year to investigate the effect of PPI administration on the efficacy of cancer i mmunotherapy (35,36) (20,23,27) . And we did a more detailed subgroup analysis, and even reached some conclusions d ifferent from the previous two studies.…”

Section: Discussionmentioning

confidence: 99%

Concomitant of Proton Pump Inhibitors is Associated with Poor Clinical Outcomes in Patients Treated with Immune Checkpoint Inhibitors ：An Up-to-date Systematic Review and Meta-analysis

Mao

Tong

Yan

et al. 2021

Preprint

View full text Add to dashboard Cite

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.

show abstract

“…A recent systematic review that included seven studies reported a null association between PPI use and mortality risk (HR = 1.05; 95% CI = 0.79-1.40); however, concomitant PPI use played contrary roles in patients with different cancer types, demonstrating a beneficial effect in melanoma patients and a negative effect in NSCLC patients. 24 While the mechanisms underlying the inconsistent clinical consequences of PPI use in melanoma and NSCLC is yet to be elucidated, it has been hypothesized that the immunosuppressive effect of PPIs may have exerted an excessive influence on the prognosis of NSCLC patients who are already susceptible to infections, including pneumonia. 20,24,25 Consistent with our findings, three retrospective post hoc analyses of RCTs of atezolizumab also demonstrated negative survival outcomes associated with concurrent PPI use.…”

Section: Discussionmentioning

confidence: 99%

“…24 While the mechanisms underlying the inconsistent clinical consequences of PPI use in melanoma and NSCLC is yet to be elucidated, it has been hypothesized that the immunosuppressive effect of PPIs may have exerted an excessive influence on the prognosis of NSCLC patients who are already susceptible to infections, including pneumonia. 20,24,25 Consistent with our findings, three retrospective post hoc analyses of RCTs of atezolizumab also demonstrated negative survival outcomes associated with concurrent PPI use. One study identified 757 atezolizumab users (234 PPI users and 523 PPI nonusers) using pooled RCT data of patients with NSCLC and reported an increased mortality risk in PPI users (HR = 1.45; 95% CI = 1.20-1.75).…”

Section: Discussionmentioning

confidence: 99%

Survival outcomes of patients with nonsmall cell lung cancer concomitantly receiving proton pump inhibitors and immune checkpoint inhibitors

Baek

Kang

Hong

et al. 2021

Intl Journal of Cancer

View full text Add to dashboard Cite

Recent evidence suggests that gut microbiota dysbiosis adversely affects the efficacy of immune checkpoint inhibitors (ICIs). Our objective was to investigate the association between concomitant use of proton pump inhibitors (PPIs) and ICIs, and poor prognosis in patients with nonsmall cell lung cancer (NSCLC). We conducted a cohort study using a completely enumerated lung cancer cohort from a nationwide healthcare database in South Korea. We identified 2963 patients treated with ICIs as second-line or later therapy for stage ≥IIIB NSCLC. PPI use was ascertained within 30-days before and on the date of ICI initiation, and nonuse was defined as no prescription of PPIs during this period. Using national vital statistics in South Korea, we assessed the risk of all-cause mortality associated with concomitant PPI use through a propensity score-matched Cox proportional hazard model. Among 1646 patients included after 1:1 propensity score-matching, concomitant PPI use was associated with a 28% increased risk of all-cause mortality, compared to nonuse (adjusted hazard ratio [HR] 1.28; 95% confidence intervals [CIs],1.13-1.46). We observed an increased risk when we restricted the analysis to new users of PPI (adjusted HR = 1.64; 95% CI = 1.25-2.17). Subgroup analysis showed that PPI use was associated with high mortality risk among patients with viral hepatitis (adjusted HR = 2.72; 95% CI = 1.54-4.78; P interaction = .048). Our study indicates that PPI use is associated with poor prognosis in NSCLC patients treated with ICIs. Further prospective studies are required to determine the risk-benefit balance of concomitant use of PPIs and ICIs.

show abstract

The association between proton pump inhibitors use and clinical outcome of patients receiving immune checkpoint inhibitors therapy

Cited by 28 publications

References 26 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

Concomitant of Proton Pump Inhibitors is Associated with Poor Clinical Outcomes in Patients Treated with Immune Checkpoint Inhibitors ：An Up-to-date Systematic Review and Meta-analysis

Survival outcomes of patients with nonsmall cell lung cancer concomitantly receiving proton pump inhibitors and immune checkpoint inhibitors

Contact Info

Product

Resources

About