(CHICAGO, IL) — Data from a detailed follow-up of patients with resected renal cell carcinoma (RCC) and normal ejection fraction who received adjuvant sunitinib or sorafenib has led investigators to conclude that neither agent is associated with significant cardiac dysfunction, according to a presentation at the 2012 American Society of Clinical Oncology Annual Meeting.

Reports of cardiac dysfunction range from 1% to 28% with use of tyrosine kinase inhibitors (TKIs). Mechanism of action is believed to be myocyte metabolic dysfunction. Sunitinib is the best characterized agent; however, most analyses are retrospective, said Naomi B. Haas, MD, of the Abramson Cancer Center at the University of Pennsylvania, Philadelphia.

She presented results of the largest prospective study ever performed of cardiac events of TKIs, an analysis of the phase 3 randomized Eastern Cooperative Oncology Group trial E2805, Adjuvant Sorafenib or Sunitinib in Unfavorable REnal cell carcinoma (ASSURE). This study sought to determine if patients treated with sunitinib or sorafenib had clinically significant decreases in left ventricular (LV) ejection fraction (EF) and to describe the frequency of clinically significant heart failure.

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EF was measured by Multi Gated Acquisition (MUGA) scan at baseline, 3, 6, and 12 months (ie, end of treatment and completion of study); if symptoms developed; and at 3 months after the last abnormal assessment. Primary cardiac end point was EF decline less than the institutional lower limit of normal (ILN) that was a ≥16% decline from baseline, and that occurred ≤6 months into therapy, Dr. Haas explained.

Clinically significant heart failure was grade 3 or higher LV systolic or diastolic dysfunction, defined as severe symptoms with any activity or from drop in EF responsive (grade 3) or refractory (grade 4) to therapy. Late LVEF events were defined as a drop in LVEF of ≥16% occurring after 6 months of treatment.

Post-baseline MUGAs were available for 1,589 of 1,943 patients accrued in the trial; 1,293 had an event in 6 months or were followed by MUGA for 6 months. A total of 21 patients had primary events: nine of 397 (2.3%) assessed in the sunitinib arm, seven of 394 (1.8%) in the sorafenib arm, and five of 502 (1.0%) in the placebo arm. Of these patients, 14 (66.7%) had a very high RCC recurrence risk; 19 (90.5%) had clear cell; 14 (66.7%) had a performance status of 0; 16 (76.2%) were male; 17 (81.0%) were age >65 years; and 8 (38.1%) had a prior cardiovascular history. Five grade 3 LV systolic events occurred in the sunitinib arm, four in the sorafenib arm, and two in the placebo arm. Eight patients had cardiac ischemia that was possibly or probably due to treatment with the respective agent

“Ischemic events were uncommon and not clearly associated with treatment,” Dr. Haas said, adding that LV dysfunction was found to be reversible. Further prospective study on the effects of these agents is needed in patients who have preexisting dysfunction.

Neither sunitinib nor sorafenib have cardiac contradictions for use in the adjuvant setting.