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

초록

Background: Recent evidence suggests that gut microbiota dysbiosisadversely affects the efficacy of immune checkpoint inhibitors. Theassociation between the concomitant use of proton pump inhibitorswith immune checkpoint inhibitors and poor prognosis remainscontroversial.Objectives: To investigate the association between concomitant useof proton pump inhibitors and immune checkpoint inhibitors and poorprognosis in patients with non-small cell lung cancer.Methods: We conducted a cohort study using a completely enumer-ated lung cancer cohort from a nationwide healthcare database inSouth Korea. We identified 2,963 patients treated with immunecheckpoint inhibitors as second-line or above therapy for stage ≥ IIIBnon-small cell lung cancer. Proton pump inhibitor use wasascertained within 30 days before and on the date of immune check-point inhibitor ini tiation, and non-use was defined as no prescriptionof proton pump inhibitors during this period. We assessed the risk ofall-cause mortality, using national vital statistics in South Korea,associated with concom itant proton pump inhibitor use using a pro-pensity scor e-matched Cox proportional hazard model and Kaplan–Meier survival.Results: Among 1,646 patients included after 1:1 propensity score-matching, concomitant proton pump inhibitor use was associated witha 28% increased risk of all-cause mortality compared to non-use(adjusted hazard ratio, 1.28; 95% confidence interval, 1.13-1.46). Weobserved an increased risk when we restricted the analysis to newusers of proton pump inhibitors (adjusted hazard ratio, 1.64; 95% con-fidence interval, 1.25-2.17). Subgroup analysis showed that protonpump inhibitor use was associated with a particularly prominent mor-tality risk among patients with viral hepatitis (adjusted hazard ratio,2.72; 95% confidence interval, 1.54-4.78; p for interaction, 0.048).Conclusions: Our study indicates that proton pump inhibitor use isassociated with poor prognosis in non-small cell lung cancer patientstreated with immune checkpoint inhibitors. The risk-benefit balanceof the concomitant use of proton pump inhibitors and immune check-point inhibitors warrants careful consideration.