Tyrosine kinase-targeting drugs-associated heart failure

Br J Cancer. 2017 May 9;116(10):1366-1373. doi: 10.1038/bjc.2017.88. Epub 2017 Apr 11.

Abstract

Background: The impact of cancer therapies on cardiac disease in the general adult cancer survivor population is largely unknown. Our objective was to evaluate which tyrosine kinase-targeting drugs are associated with greater risk for new-onset heart failure (HF).

Methods: A nested case-control analysis was conducted within a cohort of 27 992 patients of Clalit Health Services, newly treated with a tyrosine kinase-targeting, and/or chemotherapeutic drug, for a malignant disease, between 1 January 2005 and 31 December 2012. Each new case of HF was matched to up to 30 controls from the cohort on calendar year of cohort entry, age, gender, and duration of follow-up. Main outcome measure was odds ratio (OR) with 95% confidence interval (CI) of new-onset HF.

Results: There were 936 incident cases of HF during 71 742 person-years of follow-up. Trastuzumab (OR 1.90, 95% CI 1.46-2.49), cetuximab (OR 1.72, 1.10-2.69), panitumumab (OR 3.01, 1.02-8.85), and sunitinib (OR 3.39, 1.78-6.47) were associated with increased HF risk. Comorbidity independently associated with higher risk in a multivariable conditional regression model was diabetes mellitus, hypertension, chronic renal failure, ischaemic heart disease, valvular heart disease, arrhythmia, and smoking.

Conclusions: Trastuzumab, cetuximab, panitumumab, and sunitinib are associated with increased risk for new-onset HF.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / adverse effects
  • Antineoplastic Agents / adverse effects*
  • Case-Control Studies
  • Cetuximab / adverse effects
  • Cohort Studies
  • Heart Failure / epidemiology*
  • Humans
  • Incidence
  • Indoles / adverse effects
  • Israel / epidemiology
  • Middle Aged
  • Neoplasms / drug therapy*
  • Odds Ratio
  • Panitumumab
  • Protein Kinase Inhibitors / adverse effects*
  • Pyrroles / adverse effects
  • Risk Factors
  • Sunitinib
  • Trastuzumab / adverse effects

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Indoles
  • Protein Kinase Inhibitors
  • Pyrroles
  • Panitumumab
  • Trastuzumab
  • Cetuximab
  • Sunitinib