Impact of lenvatinib on renal function: long-term analysis of differentiated thyroid cancer patients

BMC Cancer. 2021 Aug 5;21(1):894. doi: 10.1186/s12885-021-08622-w.

Abstract

Background: Because lenvatinib is well known to induce proteinuria by blocking the vascular endothelial growth factor (VEGF) pathway, renal function is a concern with long-term administration of lenvatinib. The long-term effects of lenvatinib on renal function in patients with advanced differentiated thyroid carcinoma (DTC) were analyzed.

Method: This study involved 40 DTC patients who continued lenvatinib therapy for ≥6 months. Estimated glomerular filtration rate (eGFR) was calculated as an indicator of renal function. The temporal course of eGFR, effects of baseline eGFR on eGFR changes, and factors affecting renal impairment were investigated.

Results: The overall cohort showed sustainable decreases in eGFR, with decreased values of 11.4, 18.3, and 21.0 mL/min/1.73 m2 at 24, 36, and 48 months after starting treatment, respectively. No differences in eGFR decrease every 6 months were seen for three groups classified by baseline eGFR ≥90 mL/min/1.73 m2 (n = 6), < 90 but ≥60 mL/min/1.73 m2 (n = 26), or < 60 but ≥45 mL/min/1.73 m2 (n = 8). Grade 3 proteinuria was associated with declines in eGFR (p = 0.0283). Long observation period was also associated with decreases in eGFR (p = 0.0115), indicating that eGFR may decrease in a time-dependent manner.

Conclusion: Lenvatinib can induce declines in eGFR, particularly with treatment duration > 2 years, regardless of baseline eGFR. Proteinuria is a risk factor for declines in eGFR. Patients who start lenvatinib with better renal function show a renal reserve capacity, prolonging clinical outcomes. Decision-making protocols must balance the benefits of lenvatinib continuation with acceptable risks of harm.

Keywords: Advanced thyroid carcinoma; Lenvatinib; Proteinuria; Renal function; eGFR.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney / drug effects*
  • Kidney Diseases / diagnosis
  • Kidney Diseases / epidemiology
  • Kidney Diseases / etiology
  • Kidney Diseases / physiopathology
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Phenylurea Compounds / adverse effects*
  • Phenylurea Compounds / therapeutic use
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Quinolines / adverse effects*
  • Quinolines / therapeutic use
  • Thyroid Neoplasms / complications
  • Thyroid Neoplasms / drug therapy
  • Thyroid Neoplasms / epidemiology
  • Time Factors
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Quinolines
  • Vascular Endothelial Growth Factor A
  • lenvatinib