Proton Pump Inhibitors Linked to Poor Survival Outcomes in Gastric Cancer Patients

Strategic Insights -

A study published in the British Journal of Clinical Pharmacology has found that proton pump inhibitors (PPIs) are associated with shorter progression-free survival in patients with advanced gastric cancer receiving ramucirumab, a vascular endothelial growth factor receptor 2 (VEGFR2)-targeting monoclonal antibody, plus paclitaxel or nab-paclitaxel.

Researchers from the University of Tsukuba Hospital conducted a retrospective study of 152 patients with advanced gastric cancer receiving ramucirumab plus paclitaxel or nab-paclitaxel as a second-line therapy. The study found that patients who used PPIs had a median progression-free survival (PFS) of 3.7 months, compared to 4.7 months for those who did not use PPIs (hazard ratio: 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, also identified PPI use as a prognostic factor for PFS (hazard ratio: 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.

Key Takeaways:

  • The study included 152 patients with advanced gastric cancer receiving ramucirumab plus paclitaxel or nab-paclitaxel as a second-line therapy.
  • Patients who used PPIs had a shorter median progression-free survival (PFS) compared to those who did not use PPIs (3.7 months vs. 4.7 months).
  • Multivariate analysis adjusted for age, the Glasgow prognostic score, total gastrectomy, and massive ascites identified PPI use as a prognostic factor for PFS.
  • Serum VEGF-A concentrations were higher in PPI users than in non-PPI users at baseline and during ramucirumab therapy.
  • The study concluded that concomitant PPI use was associated with worse survival outcomes in patients with advanced gastric cancer receiving ramucirumab plus paclitaxel or nab-paclitaxel.
  • The study's lead author was Kosuke Doki from the University of Tsukuba Hospital.
  • The study's co-authors included Takuya Kaneko, Takeshi Yamada, Masato Uda, Yoshiyuki Yamamoto, Mariko Kobayashi, Kiichiro Tsuchiya, and Masato Homma.

Statistics:

  • Median progression-free survival (PFS) was 3.7 months for PPI users and 4.7 months for non-PPI users.
  • Hazard ratio for PFS was 1.44 (95% CI: 1.01-2.06; P = 0.040) for PPI users compared to non-PPI users.
  • Hazard ratio for PFS was 1.48 (95% CI: 1.02-2.14; P = 0.038) for PPI use as a prognostic factor for PFS after multivariate analysis.

Sources:

  • Association of concomitant proton pump inhibitor use with worse survival outcomes in patients with advanced gastric cancer receiving ramucirumab. British Journal of Clinical Pharmacology, 2025.
  • University of Tsukuba Hospital.
  • Kosuke Doki, Dept. of Pharmacy, University of Tsukuba, Ibaraki, Japan.
  • Takuya Kaneko, Takeshi Yamada, Masato Uda, Yoshiyuki Yamamoto, Mariko Kobayashi, Kiichiro Tsuchiya, and Masato Homma.