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

Cardiovascular events among 1090 cancer patients treated with sunitinib, interferon, or placebo: a comprehensive adjudicated database analysis demonstrating clinically meaningful reversibility of cardiac events.

Author information

1
The University of Texas MD Anderson Cancer Center, Houston, TX, United States. Electronic address: mewer@mdanderson.org.
2
Bern University Hospital, Bern, Switzerland.
3
Vanderbilt Heart and Vascular Institute, Nashville, TN, United States.
4
Pfizer Oncology, New York, NY, United States.
5
Ludwig Center at Harvard, Dana-Farber Cancer Institute Sarcoma Center, and Harvard Medical School, Boston, MA, United States.
6
Memorial Sloan-Kettering Cancer Center, New York, NY, United States.

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

PMID:
24930624
DOI:
10.1016/j.ejca.2014.05.013
[Indexed for MEDLINE]

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