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

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 efficacy 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.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.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.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.