Cardiovascular Events Among 1090 Cancer Patients Treated With Sunitinib, Interferon, or Placebo: A Comprehensive Adjudicated Database Analysis Demonstrating Clinically Meaningful Reversibility of Cardiac Events

Eur J Cancer. 2014 Aug;50(12):2162-70. doi: 10.1016/j.ejca.2014.05.013. Epub 2014 Jun 12.

Abstract

Purpose: To define cardiovascular (CV) risk and reversibility of cardiac events in patients who received sunitinib versus comparator treatment (interferon-alfa or placebo).

Patients and methods: We performed a retrospective adjudication of comprehensive CV adverse events (AEs) from two phase 3 trials. Components of the comprehensive CV AE end-point comprised hypertension, symptomatic and asymptomatic left ventricular ejection fraction decreases (SD-LVEF; AD-LVEF) and extent of reversibility, heart-failure symptoms, thromboembolic events, dysrhythmia and CV death. Three cardiologists and one oncologist, blinded to treatment allocation, adjudicated suspected CV AEs in the pooled trial database (N=1090).

Results: Incidence rates (IR) for sunitinib versus Interferon-alfa (IFN-α)/placebo were hypertension: 6.9 versus 2.6 (hazard ratio (HR), 3.1; 95% confidence interval (CI), 2.4-4.0); SD-LVEF: 0.4 versus 0.2 (HR, 2.5; 95% CI, 1.0-6.2); AD-LVEF: 1.1 versus 0.8 (HR, 2.1; 95% CI, 1.3-3.4); and composite CV AE end-point: 10.1 versus 4.8 (HR, 2.5; 95% CI, 2.0-3.1), however reversibility, not previously quantified, was found to be clinically meaningful.

Conclusions: Hypertension and SD-LVEF/AD-LVEF were significantly higher with sunitinib versus IFN-α/placebo. Among patients who experienced a cardiac event, symptomatic and asymptomatic instances of decreased cardiac dysfunction were adjudicated as reversible in 47 of 83 (56%) and 17 of 30 (57%), respectively. Among sunitinib-treated patients, many were able to resume sunitinib dosing following resolution of events, a finding that is important for clinical care. In comparator groups, symptomatic and asymptomatic instances were adjudicated as reversible in 4 of 6 (66.7%) and 11 of 21 (52%), respectively. Thromboembolic, dysrhythmic and/or CV deaths were not significantly higher in sunitinib-treated patients.

Keywords: Cancer treatment-related hypertension; Cardiotoxicity; Reversibility of cardiotoxic events; Sunitinib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / adverse effects*
  • Antineoplastic Agents / adverse effects*
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / epidemiology
  • Clinical Trials, Phase III as Topic
  • Humans
  • Hypertension / chemically induced
  • Hypertension / epidemiology
  • Incidence
  • Indoles / adverse effects*
  • Interferon-alpha / adverse effects*
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasms / complications
  • Neoplasms / drug therapy*
  • Pyrroles / adverse effects*
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Risk Factors
  • Sunitinib

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Indoles
  • Interferon-alpha
  • Pyrroles
  • Sunitinib