The effect of proton pump inhibitor uses on outcomes for cancer patients treated with immune checkpoint inhibitors: a meta-analysis

Li, Chao; Xia, Zhengzheng; Li, Anna; Meng, Jiao

doi:10.21037/atm-20-7498

Cited by 32 publications

(40 citation statements)

References 30 publications

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“…Li C et al conducted a meta-analysis including 1,167 cancer patients to investigate the impact of PPI use on the survival of cancer patients treated with ICI, suggesting concomitant ICI-PPI therapy does not appear to be significantly associated with ICI efficacy. 32 However, the impact of PPI use on ICI efficacy remains poorly defined due to the small sample size. In the past year, the effect of PPI use on ICI efficacy has been investigated in several global large-scale clinical trials including IMvigor210/IMvigor211 trials.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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Background: The present study aimed to evaluate the effects of concomitant proton pump inhibitor (PPI) use on immune checkpoint inhibitor (ICI) efficacy among advanced cancer patients. Methods and Materials: A systematic literature search of electronic database was performed to identify all potential reports. Then, meta-analyses were conducted to obtain pooled HRs with 95% CIs, which reveal the influence of PPI use on PFS and OS in patients receiving ICI treatment. Results: A total of 7 studies with 3,647 advanced cancer patients fulfilled the inclusion criteria. The impact of PPI use was then evaluated on 3,340 patients for PFS and 3,647 patients for OS. Concomitant PPI use has a detrimental effect on the efficacy of ICIs that PPI use increased the risk of progression by 28% (HR = 1.28, 95% CI 1.17-1.40; I2 = 31.3%, Q test P = .21) when compared to those not receiving PPIs. Similarly, the meta-analysis showed that PPI use was also associated with shorter OS of advanced cancer patients receiving ICIs that PPI use increased risk of death by 39% (HR = 1.39, 95% CI 1.26-1.54; I2 = 36.5%, Q test P = .16). Sensitivity analysis showed that the pooled HRs were constant after excluding one study at a time, and no significant publication biases were detected. Conclusion:The meta-analysis suggested that concomitant PPI use is significantly associated with low clinical benefit in ICI treatment, revealing a significantly reduced PFS and OS in advanced cancer patients receiving ICIs who are also exposed to PPI.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…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

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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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“…Similar results were also reported in several studies raising concerns about the use of PPIs in cancer patients treated with CPIs [ 87 , 89 ]. On the other side, other studies failed to conclude a causal relationship between the use of PPIs and worse outcomes in patients with cancer treated with CPIs [ 90 , 91 ]. Given this controversy, it remains debatable whether the use of PPIs could influence the response to CPIs, and carefully assessing the need of PPIs should be done before randomly or routinely prescribing them to cancer patients.…”

Section: Gut Microbiota’s Influence On Patients’ Response and Sensitivity To Cpismentioning

confidence: 99%

The Role of Gut Microbiota in Overcoming Resistance to Checkpoint Inhibitors in Cancer Patients: Mechanisms and Challenges

Bouferraa

Chedid

Amhaz

et al. 2021

IJMS

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The introduction of immune checkpoint inhibitors has constituted a major revolution in the treatment of patients with cancer. In contrast with the traditional cytotoxic therapies that directly kill tumor cells, this treatment modality enhances the ability of the host’s immune system to recognize and target cancerous cells. While immune checkpoint inhibitors have been effective across multiple cancer types, overcoming resistance remains a key area of ongoing research. The gut microbiota and its role in cancer immunosurveillance have recently become a major field of study. Gut microbiota has been shown to have direct and systemic effects on cancer pathogenesis and hosts anti-tumor immune response. Many studies have also shown that the host microbiota profile plays an essential role in the response to immunotherapy, especially immune checkpoint inhibitors. As such, modulating this microbial environment has offered a potential path to overcome the resistance to immune checkpoint inhibitors. In this review, we will talk about the role of microbiota in cancer pathogenesis and immune-system activity. We will also discuss preclinical and clinical studies that have increased our understanding about the roles and the mechanisms through which microbiota influences the response to treatment with immune checkpoint inhibitors.

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The effect of proton pump inhibitor uses on outcomes for cancer patients treated with immune checkpoint inhibitors: a meta-analysis

Cited by 32 publications

References 30 publications

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

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

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

The Role of Gut Microbiota in Overcoming Resistance to Checkpoint Inhibitors in Cancer Patients: Mechanisms and Challenges

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