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

Aims 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. Methods 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. Results 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. Conclusions 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.