Association of concomitant proton pump inhibitor use with worse survival outcomes in patients with advanced gastric cancer receiving ramucirumab.

Vascular endothelial growth factor (VEGF)-A binding to VEGF receptor (VEGFR)2 promotes tumour angiogenesis and progression. Proton pump inhibitors (PPIs) upregulate VEGF-A expression in various cancers. This study examined the association between concomitant PPI use and survival outcomes in patients with advanced gastric cancer (AGC) receiving ramucirumab, a VEGFR2-targeting monoclonal antibody, plus paclitaxel (PTX) or nab-paclitaxel (nab-PTX). The impact of PPI use on serum VEGF-A concentrations was also evaluated. This retrospective study included 152 patients with AGC receiving ramucirumab plus PTX/nab-PTX as a second-line therapy. Progression-free survival (PFS) was compared between PPI and non-PPI users. Multivariate Cox proportional hazards analysis was used to assess the prognostic factors for PFS. Serum VEGF-A concentrations were measured in blood samples from 25 patients at baseline and on Day 14 following the first ramucirumab infusion. Median PFS was 3.7 months (95% confidence interval [CI]: 2.8-4.7) for PPI users and 4.7 months (95% CI: 4.0-5.3) for non-PPI users (hazard ratio [HR]: 1.44; 95% CI: 1.01-2.06; P = 0.040). Multivariate analysis, adjusted for age, the Glasgow prognostic score, total gastrectomy and massive ascites, identified PPI use as a prognostic factor for PFS (HR: 1.48; 95% CI: 1.02-2.14; P = 0.038). Serum VEGF-A concentrations were higher in PPI users than in non-PPI users at baseline and during ramucirumab therapy. Concomitant PPI use was associated with shorter PFS in patients with AGC receiving ramucirumab plus PTX/nab-PTX, likely due to elevated serum VEGF-A concentrations during treatment.