The association between proton pump inhibitor use and systemic anti‐tumour therapy on survival outcomes in patients with advanced non‐small cell lung cancer: A systematic review and meta‐analysis

Abstract

Aims Proton pump inhibitors (PPIs) are often prescribed to prevent or treat gastrointestinal disease. Whether the combination of systemic anti‐tumour therapy and PPIs leads to poor outcomes in patients with advanced non‐small cell lung cancer (NSCLC) is unclear. This systematic review explored the relationship between PPIs and survival outcomes of patients with advanced NSCLC who are receiving systemic anti‐tumour therapy. Methods We searched studies reporting the overall survival (OS) and/or progression‐free survival (PFS) of advanced NSCLC patients who are receiving systemic anti‐tumour therapy with or without PPIs on PubMed, EMBASE and the Cochrane Library for literature published prior to 31 August 2021. The meta‐analysis used a random effects model to estimate the hazard ratio (HR) with 95% confidence intervals (CI) and I2 to assess statistical heterogeneity. Publication bias and sensitivity analysis were performed. Results Fourteen retrospective studies comprising 13 709 advanced NSCLC patients were identified. Subgroup analyses showed that the use of PPI was correlated with the OS or PFS of patients receiving chemotherapy, targeted therapy, and immunotherapy (PPI users' group vs non‐users' group: HR for OS = 1.35, 95% CI = 1.21–1.51, P < .00001; HR for PFS = 1.50, 95% CI = 1.25–1.80, P < .0001). Publication bias and sensitivity analyses confirmed that the results were robust. Conclusion Meta‐analysis demonstrated that PPI use in advanced NSCLC patients who were undergoing systemic anti‐tumour therapy was correlated with increased mortality risk. Until results are further confirmed, caution should be applied when administering PPIs and systemic anti‐tumour therapy to advanced NSCLC patients.

The Correlation between the Use of the Proton Pump Inhibitor and the Clinical Efficacy of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

“…On the one hand, compared with the study of Wei et al, Li et al, Qin et al, and Sophia et al [ 10 , 15 , 23 , 24 ], this study included more studies on NSCLC ( n = 11 vs. n = 6 for Wei et al, n = 7 for Li et al, n = 7 for Qin et al, n = 4 for Sophia et al) and more patients ( n = 7,893 vs. n = 5,114 for Wei et al, n = 1,428 for Li et al, n = 3,647 for Qin et al, n = 2,940 for Sophia et al), especially including two articles published in 2022. On the other hand, based on more factors, like the duration of exposure to PPI, the PPI treatment, type of ICIs treatment, sample size, age, and region, the subgroup analysis was conducted.…”

“…First, PPI has been proved to play a pivotal role in operating the immunologic defense to the treatment of tumors by regulating the activity or compositions of the gastrointestinal bacteria [ 18 ]. Second, for patients with gastric ulcers or gastrointestinal bleeding history, PPI could be prophylactically used to prevent the occurrence of stress ulcers [ 10 ]. Third, since PPI could greatly increase the sensitivity of cancer patients to chemotherapy, it was often used together with other types of anticancer drugs, such as ICIs, nonetheless, the clinical efficacy of the combination has remained unknown until today.…”

“…First, PPI has been proved to play a pivotal role in operating the immunologic defense to the treatment of tumors by regulating the activity or compositions of the gastrointestinal bacteria [18]. Second, for patients with gastric ulcers or gastrointestinal bleeding history, PPI could be prophylactically used to prevent the occurrence of stress ulcers [10].…”

“…On the one hand, compared with the study of Wei et al, Li et al, Qin et al, and Sophia et al [10,15,23,24], this study included more studies on NSCLC (n � 11 vs. n � 6 for Wei [15,25] in 2020. is could be due to the fact that the PPI use would lead to greater changes in the activity and composition of the gastrointestinal microbiota, which would be related to the tolerance of the T-cells. Simultaneously, the PPI use would not only affect the microbiota of gastrointestinal tract, but also would have a certain impact on the growth, metastasis, and progression of the tumor.…”

“…In recent years, since PPI could enhance the sensitivity of cancer patients towards chemotherapy, hence, it has gained prominence in the field of tumor treatment [ 8 , 9 ]. Nevertheless, the efficacy and risk of the use of PPI are different for various cancer types [ 10 ]. However, the efficacy of the use of PPI in the treatment of cancer is not very clear, and needs further research.…”