Prospective evaluation of sunitinib-induced cardiotoxicity in patients with metastatic renal cell carcinoma

Vivek Narayan, Stephen Keefe, Naomi Haas, Le Wang, Igor Puzanov, Mary Putt, Anna Catino, James Fang, Neeraj Agarwal, David Hyman, Amanda M. Smith, Brian S. Finkelman, Hari K. Narayan, Steven Ewer, Chantal ElAmm, Daniel Lenihan, Bonnie Ky

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Abstract

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.

Original languageEnglish
Pages (from-to)3601-3609
Number of pages9
JournalClinical Cancer Research
Volume23
Issue number14
DOIs
StatePublished - Jul 15 2017
Externally publishedYes

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    Narayan, V., Keefe, S., Haas, N., Wang, L., Puzanov, I., Putt, M., Catino, A., Fang, J., Agarwal, N., Hyman, D., Smith, A. M., Finkelman, B. S., Narayan, H. K., Ewer, S., ElAmm, C., Lenihan, D., & Ky, B. (2017). Prospective evaluation of sunitinib-induced cardiotoxicity in patients with metastatic renal cell carcinoma. Clinical Cancer Research, 23(14), 3601-3609. https://doi.org/10.1158/1078-0432.CCR-16-2869