Survival outcomes of patients with nonsmall cell lung cancer concomitantly receiving proton pump inhibitors and immune checkpoint inhibitors

Recent evidence suggests that gut microbiota dysbiosis adversely affects the efficacy of immune checkpoint inhibitors (ICIs). Our objective was to investigate the association between concomitant use of proton pump inhibitors (PPIs) and ICIs, and poor prognosis in patients with nonsmall cell lung cancer (NSCLC). We conducted a cohort study using a completely enumerated lung cancer cohort from a nationwide healthcare database in South Korea. We identified 2963 patients treated with ICIs as second-line or later therapy for stage ≥IIIB NSCLC. PPI use was ascertained within 30-days before and on the date of ICI initiation, and nonuse was defined as no prescription of PPIs during this period. Using national vital statistics in South Korea, we assessed the risk of all-cause mortality associated with concomitant PPI use through a propensity score-matched Cox proportional hazard model. Among 1646 patients included after 1:1 propensity score-matching, concomitant PPI use was associated with a 28% increased risk of all-cause mortality, compared to nonuse (adjusted hazard ratio [HR] 1.28; 95% confidence intervals [CIs], 1.13-1.46). We observed an increased risk when we restricted the analysis to new users of PPI (adjusted HR = 1.64; 95% CI = 1.25-2.17). Subgroup analysis showed that PPI use was associated with high mortality risk among patients with viral hepatitis (adjusted HR = 2.72; 95% CI = 1.54-4.78; P_interaction =.048). Our study indicates that PPI use is associated with poor prognosis in NSCLC patients treated with ICIs. Further prospective studies are required to determine the risk-benefit balance of concomitant use of PPIs and ICIs.