Clinical outcomes of concomitant use of proton pump inhibitors and regorafenib in patients with metastatic colorectal cancer: a multicenter study

Eur J Clin Pharmacol. 2022 Dec;78(12):1973-1979. doi: 10.1007/s00228-022-03403-1. Epub 2022 Oct 21.

Abstract

Aim: To compare survival outcomes, response rates, and adverse events (AEs) in proton pump inhibitor (PPI) user and non-user patients with metastatic colorectal cancer (mCRC) treated with regorafenib.

Methods: We included 272 patients with mCRC treated with regorafenib in this study. Patients were divided into two categories according to their status of PPI use. The primary endpoint was overall survival (OS). The secondary endpoints were time to treatment failure (TTF), response rates, and safety. To exclude immortal time bias in survival analyses, we compared PPI non-user patients and all patients.

Results: There were 141 and 131 patients in the PPI non-user and user groups. Baseline characteristics were similar in each group. Pantoprazole was the most used PPI. At the median 35.2 (95% confidence interval (CI): 32.6-37.9) months follow-up, the median OS was similar in PPI non-user and all patients (6.9 months (95% CI: 5.3-8.5) and 7.7 months (95% CI:6.6-8.8), p = 0.913). TTF was also similar in PPI non-user and all patients (3.3 months (95% CI: 2.7-3.9) and 3.5 months (95% CI: 3.0-4.0), p = 0.661). In multivariable analysis, no statistically significant difference was observed between PPI user and non-user groups in OS and TTF (hazard ratio (HR), 0.99; 95% CI, 0.77-1.28; p = 0.963 for OS; HR, 0.93; 0.77-1.20, p = 0.598 for TTF). The objective response rates (ORR) were similar in the PPI non-user and user groups (19.8% and 16.8%, p = 0.455). The rates of any grade AEs were also similar in each group.

Conclusion: This study found no worse outcome in the combined use of PPI and regorafenib among patients with mCRC.

Keywords: Acid suppression; Drug-drug interactions; Regorafenib.

Publication types

  • Multicenter Study

MeSH terms

  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • Humans
  • Phenylurea Compounds / adverse effects
  • Proton Pump Inhibitors / adverse effects
  • Rectal Neoplasms* / drug therapy
  • Survival Rate

Substances

  • regorafenib
  • Proton Pump Inhibitors
  • Phenylurea Compounds