Potassium-competitive acid blocker has more negative impacts on clinical outcomes in patients with non-small cell lung cancer treated with checkpoint inhibitors than those of proton pump inhibitors.

Background: Proton pump inhibitors (PPIs) are well-known inducers of gut dysbiosis because oral bacteria cannot be sterilized owing to their gastric acid-suppressing effect. PPI-induced gut dysbiosis is associated with shorter progression-free survival (PFS) and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Although vonoprazan exhibits more powerful acid suppression than PPIs, its effect on ICI therapy outcomes remains unknown. We evaluated vonoprazan on ICI therapy efficacy in patients with NSCLC.

Methods: This retrospective study included patients aged ≥ 18 years with advanced or recurrent NSCLC receiving ICI monotherapy or ICI plus chemotherapy between January 2016 and December 2021 at Osaka Metropolitan University Hospital.

Results: Of the 289 patients, 121 received PPIs, 22 received vonoprazan, and 146 did not receive either vonoprazan or PPIs (control group). In multivariate analysis, the PFS in the PPI (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.21-2.21; p = 0.0014) and vonoprazan groups (HR, 2.49; 95% CI, 1.47-4.23; p < 0.001) were significantly shorter than those in the control group. The OS in the PPI (HR, 1.74; 95% CI, 1.23-2.45; p = 0.0017) and vonoprazan groups (HR, 5.24; 95% CI, 2.88-9.53; p < 0.001) were also significantly shorter than those in the control group.

Conclusions: Vonoprazan was associated with worse PFS and OS in patients with NSCLC treated with ICIs than those who did not receive PPIs or vonoprazan. Moreover, vonoprazan may have a more negative impact on ICI therapy efficacy than PPI.