Impact of Concomitant Proton Pump Inhibitor Use on Oncologic Outcomes of Neoadjuvant Chemoimmunotherapy in Locally Advanced Gastric Cancer: A Multicenter Real-World Study.

Abstract

Neoadjuvant chemoimmunotherapy (NCIT) is an important treatment strategy for locally advanced gastric cancer (LAGC). Although proton pump inhibitors (PPIs) are frequently prescribed in oncology settings, their impact on the efficacy of perioperative immunotherapy remains unclear. This multicenter retrospective cohort study included 107 patients with LAGC who received NCIT followed by curative-intent gastrectomy (January 2020‒December 2023). Patients receiving potassium-competitive acid blockers were included in the PPI group. Clinicopathological characteristics, pathological response, disease-free survival (DFS), and overall survival (OS) were compared, and multivariable Cox regression models identified independent prognostic factors. The PPI group comprised 48 (44.9%) patients. Baseline characteristics were generally balanced between groups. PPI exposure was associated with significantly reduced nodal clearance, reflected by a lower ypN0 rate (47.9% versus 67.8%, p = 0.038). After a median follow-up of 33.0 months, DFS and OS were significantly worse in PPI-treated patients. Median DFS was 40.0 months (95% confidence interval [CI], 22.9-57.0) in the PPI group and not reached in the non-PPI group (p = 0.001). Multivariable analysis identified PPI exposure as an independent predictor of inferior DFS (hazard ratio [HR] 2.60; p = 0.033) and OS (HR 4.41; p = 0.007). Concomitant PPI exposure during NCIT was associated with impaired pathological nodal response and worse long-term survival in patients with LAGC. Given the retrospective design and limited data on exposure timing and duration, these findings should be considered hypothesis-generating and should not be interpreted as evidence of a duration-dependent or causal effect.