cabozantinib and Ventricular-Dysfunction--Left

The case report describes the presentation of incident heart failure with reduced ejection fraction, following Cabozantinib chemotherapy. In contrast to previous cases, despite maximal medical therapy for this gentleman it became irreversible and contributed to his death. Hence the case illustrates the potential cardiotoxicity of Cabozantinib and reinforces the need for co-ordinated multi-disciplinary team care for such patients. Within existing cardio-oncology infrastructure, it may mean that such patients require enhanced echocardiographic surveillance.

Topics: Anilides; Heart Failure; Humans; Neoplasms; Ventricular Dysfunction, Left

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.. 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.. 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).. 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.

Topics: Aged; Anilides; Antineoplastic Agents; Biomarkers; Carcinoma, Renal Cell; Cardiotoxicity; Female; Humans; Incidence; Italy; Kidney Neoplasms; Male; Natriuretic Peptide, Brain; Prospective Studies; Protein Kinase Inhibitors; Pyridines; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Troponin I; Ventricular Dysfunction, Left; Ventricular Function

Cabozantinib is a multitargeted tyrosine kinase inhibitor, with activity against vascular endothelial growth factor receptor, as well as MET, RET, and AXL. It is currently approved for treating advanced thyroid and kidney cancers, and is being investigated in other cancers. We present a case of reversible heart failure due to cabozantinib use in a 70-year-old man with metastatic renal cell carcinoma. This is, to our knowledge, one of the first reported cases of cardiomyopathy associated with cabozantinib use.

Topics: Aged; Anilides; Carcinoma, Renal Cell; Heart Failure; Humans; Kidney Neoplasms; Lung Neoplasms; Male; Protein Kinase Inhibitors; Pyridines; Ventricular Dysfunction, Left