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.
Keywords: advanced non-small cell lung cancer (NSCLC) patients; chemotherapy; immune checkpoint inhibitors (ICIs); proton pump inhibitors (PPIs); survival; tyrosine kinase inhibitors (TKIs).
© 2022 British Pharmacological Society.