Cabozantinib-related cardiotoxicity: a prospective analysis in a real-world cohort of metastatic renal cell carcinoma patients

Br J Clin Pharmacol. 2019 Jun;85(6):1283-1289. doi: 10.1111/bcp.13895. Epub 2019 Mar 31.

Abstract

Aims: Data regarding the cardiac toxicity of cabozantinib lacks. The aim of our study was to assess the risk of cabozantinib-related cardiotoxicity in mRCC patients.

Methods: We performed a multicentre prospective study on mRCC patients treated with cabozantinib between October 2016 and November 2017. Transthoracic echocardiogram and plasma biomarkers assay were assessed at baseline, 3 and 6 months after cabozantinib initiation.

Results: The study population included 22 mRCC patients. At baseline, 9.1% had a reduced left ventricular ejection fraction (LVEF), but none had a left ventricular systolic dysfunction. Patients with baseline reduced LVEF did not show further significant LVEF modification after 3 months. After 6 months, only 1 had an LVEF decline >10% compared to baseline, resulting in LV systolic dysfunction. At baseline, 64.7% and 27.3% of patients had elevated precursor brain natriuretic peptide (proBNP) and high-sensitivity troponin I (hsTnI), respectively. Among patients with basal normal proBNP and hsTnI, none had elevated values at 3 and 6 months. No correlation was found between basal elevated proBNP and basal reduced LVEF (P = .29), and between elevated proBNP and reduced LVEF after 6 months (P = .37). Similarly, we found no correlations between elevated hsTnI and reduced LVEF or elevated proBNP at baseline (P = .47; P = .38), at 3 (P = .059; P = .45) and after 6 months (P = .72; P = 1.0).

Conclusions: This prospective study revealed a modest risk of developing left ventricular systolic dysfunction related to cabozantinib. A lack of correlation between elevated cardiac biomarkers and reduced LVEF at different time-points was detected. Assessments of the cardiac function should be reserved at the occurrence of clinical symptoms.

Keywords: cabozantinib; cardiotoxicity; high-sensitivity troponin I; metastatic renal cell carcinoma; precursor brain natriuretic peptide.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Anilides / adverse effects*
  • Antineoplastic Agents / adverse effects*
  • Biomarkers / blood
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / secondary
  • Cardiotoxicity
  • Female
  • Humans
  • Incidence
  • Italy / epidemiology
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Natriuretic Peptide, Brain / blood
  • Prospective Studies
  • Protein Kinase Inhibitors / adverse effects*
  • Pyridines / adverse effects*
  • Risk Assessment
  • Risk Factors
  • Stroke Volume / drug effects
  • Time Factors
  • Troponin I / blood
  • Ventricular Dysfunction, Left / chemically induced*
  • Ventricular Dysfunction, Left / diagnosis
  • Ventricular Dysfunction, Left / epidemiology
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function / drug effects

Substances

  • Anilides
  • Antineoplastic Agents
  • Biomarkers
  • Protein Kinase Inhibitors
  • Pyridines
  • Troponin I
  • Natriuretic Peptide, Brain
  • cabozantinib