Prospective Evaluation of Sunitinib-Induced Cardiotoxicity in Patients with Metastatic Renal Cell Carcinoma

Purpose: To prospectively evaluate cardiotoxicity risk with sunitinib in metastatic renal cell carcinoma (mRCC) routine clinical practice using comprehensive echocardiography and biomarker phenotyping.

Experimental Design: In a multicenter prospective study of 90 patients with mRCC, echocardiography and biomarkers of cardiovascular injury and stress were quantified at baseline, 3.5, 15, and 33 weeks following sunitinib initiation. These "on-drug" visits corresponded to cycles 1, 3, and 6, respectively. Left ventricular (LV) dysfunction was defined as an absolute decline in LV ejection fraction (LVEF) by ≥10% to a value of <50%. Conditional survival analyses predicted the risk of LV dysfunction. Linear mixed-effects models estimated changes in LVEF, high-sensitivity Troponin I (hsTnI), and B-type natriuretic peptide (BNP) over time.

Results: The predicted risk of LV dysfunction by cycle 6 was 9.7% (95% confidence interval, 3%–17%). The majority of events occurred in the first treatment cycle. This risk diminished to 5% and 2% in patients who had not experienced dysfunction by the completion of cycles 1 and 3, respectively. All evaluable patients who experienced LV dysfunction had subsequent improvement in LVEF with careful management. Six patients (6.7%) developed hsTnI elevations >21.5 pg/mL, and 11 additional patients (12.2%) developed BNP elevations >100 pg/mL. These elevations similarly tended to occur early and resolved over time.

Conclusions: On average, patients with mRCC receiving sunitinib exhibit modest declines in LVEF and nonsignificant changes in hsTnI and BNP. However, approximately 9.7% to 18.9% of patients develop more substantive abnormalities. These changes occur early and are largely recoverable with careful management. Clin Cancer Res; 23(14); 3601–9. ©2017 AACR.

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