Cardiac effects of dovitinib in first-line metastatic renal cell carcinoma: Sub-analysis of a phase II clinical trial

Background: Dovitinib is an anti-VEGFR tyrosine kinase inhibitor (TKI) which also inhibits FGFR-1, -2, -3 and PDGFRβ. VEGFR inhibitors are known to cause cardiotoxicity. We sought to assess the cardiac effects of dovitinib in subjects with metastatic clear-cell renal cell carcinoma (mCCRCC). Methods: The 30 treatment naïve patients with mCCRCC enrolled in this single-arm, single-site, phase II study received dovitinib at 500mg 5 days on/2 days off until progression. Cardiac evaluation included; ECG (Wks 0,4,7), echocardiogram (Wks 0,12,24), lipid profile (Wks 0,4), high-sensitivity troponin T (Wks 0,4, every 6 Wks). Results: At baseline, all patients had a normal LVEF (mean 66.1% SD6.1%). At 12 Wks, the mean change in LVEF was -1.1% (SD 8.6%, p = 0.3). 13 of 18 patients that remained on treatment at 24 Wks had echocardiograms - these showed a mean drop in LVEF of -4.2% (SD 8%, p = 0.049). No patient suffered a clinical cardiac event nor symptoms. Of the five patients with positive high sensitivity troponin at baseline (range 15-49ng/ L) and the three that became positive, all had insignificant rises ( < 10ng/L or < 50% change). At 4 Wks, there was a significant rise in triglycerides (change of 1.26mmol/L SD 0.36mmol/L p = 0.0002) and significant decrease in HDL (change 0.26mmol/L SD 1.71mmol/L p = 0.0001). Conclusions: Dovitinib has sub-clinical cardiac effects not dissimilar to those observed with other anti-VEGFR TKIs. Routine use of high-sensitivity troponin T may not identify subjects who need echocardiogram surveillance on anti-VEGFR therapies.