Abstract 13485: Sunitinib and Changes in Right Ventricular Function: Insights From a Prospective Cohort of Patients With Metastatic Renal Cell Carcinoma

Abstract

Introduction: Tyrosine kinase inhibitors (TKI) have established cardiotoxic effects including hypertension and declines in left ventricular ejection fraction (LVEF). However, the effects on right ventricular (RV) function remain unknown. Methods: Patients with metastatic renal cell carcinoma (mRCC) initiating sunitinib therapy were prospectively enrolled and echocardiography was performed at baseline and at 3.5, 15 and 33 weeks. All participants with ≥ 1 echocardiographic metric of RV function (FAC, TAPSE, RV S’) from ≥2 time points were included. Estimates of mean (95% CI) absolute change in RV function and associations between clinical characteristics and changes in RV function were calculated using generalized estimating equations. Results: Of the 84 patients included, 55% had prevalent hypertension, 51% had hypercholesterolemia, 5% had heart failure and 8% had coronary heart disease. Estimates for changes in RV function after 3.5 weeks were: -0.5% (-1.5, 0.5) for FAC, p=0.32; -0.05 cm (-0.08, -0.02) for TAPSE, p=0.002; and -0.8 cm/s (-1.2, -0.5) for RV S’, p<0.001 (Figure). At 33 weeks, the decline in RV S’ remained significant (-1.8 cm/s [-2.6, -1.0], p<0.001). Higher doses of sunitinib were associated with a decline in TAPSE (50mg vs. 25mg [reference]: -0.20cm [-0.33.-0.07]). TAPSE and RV S’ were associated with concurrent declines in LVEF (-2.2% [-3.5, -0.9]; -2.1% [-3.4, -0.8] for each interquartile decline in TAPSE and RV S’ respectively, p=0.001). There were no associations between changes in FAC and LVEF, and no clinical characteristics were associated with declines in FAC. Conclusions: In patients with mRCC, sunitinib treatment was associated with a modest worsening of RV function. Further study is needed to determine the longer term consequences of these changes.