Impact of preexisting proteinuria on the development of regorafenib-induced problematic proteinuria in real-world metastatic colorectal cancer treatment

Sci Rep. 2024 Mar 2;14(1):5153. doi: 10.1038/s41598-024-55727-w.

Abstract

Regorafenib is the first multikinase inhibitor for treating metastatic colorectal cancer (mCRC). Proteinuria is a frequently encountered adverse effect, regardless of prior administration of vascular endothelial growth factor inhibitors. Herein, we aimed to assess the impact of baseline preexisting proteinuria on regorafenib-induced problematic proteinuria during real-world mCRC therapy. Patients with mCRC receiving regorafenib (n = 100) were retrospectively assessed and divided into control and preexisting proteinuria (baseline grade of 1-2) groups. The primary endpoint was the development of grade ≥ 2 (grade ≥ 3 in case of baseline grade 2 patients) proteinuria. Propensity score-matching was performed to confirm the robustness of primary analyses. Defined proteinuria occurred in 30.7 and 57.9% of patients in the control and preexisting proteinuria groups, respectively, with significant differences in the all-patient population (P = 0.01). The preexisting proteinuria group exhibited significant defined proteinuria development within 7 days of regorafenib initiation, grade ≥ 3 symptoms, and treatment suspension owing to proteinuria. Similar results were obtained in the propensity score-matched population. According to multivariate logistic regression analysis, baseline proteinuria was a singular risk factor for defined proteinuria development (adjusted odds ratio; 3.76, 95% confidence interval; 1.45-9.75, P = 0.007). Collectively, our study revealed that patients with preexisting proteinuria develop regorafenib-induced proteinuria degradation.

Keywords: Multikinase inhibitor; Preexisting proteinuria; Proteinuria; Regorafenib; Risk factor; Vascular endothelial growth factor (VEGF).

MeSH terms

  • Colonic Neoplasms* / chemically induced
  • Colorectal Neoplasms* / pathology
  • Humans
  • Phenylurea Compounds / adverse effects
  • Pyridines*
  • Rectal Neoplasms*
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A

Substances

  • regorafenib
  • Vascular Endothelial Growth Factor A
  • Phenylurea Compounds
  • Pyridines