Impact of proton-pump inhibitors on the efficacy of immune checkpoint inhibitors in non-small cell lung cancer: A systematic review and meta-analysis

Introduction: Immune checkpoint inhibitors (ICI) is a rapidly evolving treatment modality for stage IV non-small cell lung cancer (NSCLC). Concomitant proton pump inhibitor (PPI) use can potentially reduce the clinical ef-ficacy of ICIs; however, the consensus in recent literature has been conflicting. This study aims to analyze overall survival (OS) and progression-free survival (PFS) outcomes in patients with NSCLC on ICI and concomitant PPI therapy. Methods: A literature search was done in 3 databases (Pubmed/Medline, Embase, and Cochrane Central). All studies meeting the inclusion criteria assessing the impact of PPIs on the efficacy of ICI in NSCLC patients were systematically identified. A random-effects network meta-analysis evaluated OS and PFS in the two arms. Results: Four studies with 2,940 patients are included in our analysis. ICI usage alone was associated with significantly better OS [HR = 1.46, 95% CI = 1.27-1.67, P < 0.00001] and PFS [HR = 1.31, 95% CI = 1.17-1.47, P < 0.00001] when compared to concomitant PPI and ICI therapy. Conclusion: The concomitant use of PPIs during ICI therapy significantly worsens clinical outcomes with shorter OS and increased risk of disease progression in patients with NSCLC.