Cardiovascular Toxicity of Targeted Therapies for Cancer: An Overview of Systematic Reviews

Marina T Van Leeuwen; Steven Luu; Howard Gurney; Martin R Brown; Sallie-Anne Pearson; Kate Webber; Lee Hunt; Soojung Hong; Geoffrey P Delaney; Claire M Vajdic

doi:10.1093/jncics/pkaa076

Cardiovascular Toxicity of Targeted Therapies for Cancer: An Overview of Systematic Reviews

JNCI Cancer Spectr. 2020 Aug 24;4(6):pkaa076. doi: 10.1093/jncics/pkaa076. eCollection 2020 Dec.

Authors

Marina T Van Leeuwen¹, Steven Luu¹, Howard Gurney², Martin R Brown², Sallie-Anne Pearson¹, Kate Webber^{3

4}, Lee Hunt⁵, Soojung Hong^{1

6}, Geoffrey P Delaney^{7

8

9}, Claire M Vajdic¹

Affiliations

¹ Centre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales, Australia.
² Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
³ Department of Oncology, Monash Health, Clayton, Victoria, Australia.
⁴ School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
⁵ Cancer Voices NSW, Milsons Point, New South Wales, Australia.
⁶ Division of Oncology-Haematology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea.
⁷ Liverpool Cancer Therapy Centre, Liverpool, New South Wales, Australia.
⁸ Collaboration for Cancer Outcomes Research and Evaluation, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.
⁹ South Western Sydney Clinical School, University of New South Wales, Liverpool, New South Wales, Australia.

Abstract

Background: Several targeted therapies for cancer have been associated with cardiovascular toxicity. The evidence for this association has not been synthesized systematically nor has the quality of evidence been considered. We synthesized systematic review evidence of cardiovascular toxicity of individual targeted agents.

Methods: We searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews for systematic reviews with meta-analyses of cardiovascular outcomes for individual agents published to May 2020. We selected reviews according to prespecified eligibility criteria (International Prospective Register of Systematic Reviews CRD42017080014). We classified evidence of cardiovascular toxicity as sufficient, probable, possible, or indeterminate for specific cardiovascular outcomes based on statistical significance, study quality, and size.

Results: From 113 systematic reviews, we found at least probable systematic review evidence of cardiovascular toxicity for 18 agents, including high- and all-grade hypertension for bevacizumab, ramucirumab, axitinib, cediranib, pazopanib, sorafenib, sunitinib, vandetanib, aflibercept, abiraterone, and enzalutamide, and all-grade hypertension for nintedanib; high- and all-grade arterial thromboembolism (includes cardiac and/or cerebral events) for bevacizumab and abiraterone, high-grade arterial thromboembolism for trastuzumab, and all-grade arterial thromboembolism for sorafenib and tamoxifen; high- and all-grade venous thromboembolism (VTE) for lenalidomide and thalidomide, high-grade VTE for cetuximab and panitumumab, and all-grade VTE for bevacizumab; high- and all-grade left ventricular ejection fraction decline or congestive heart failure for bevacizumab and trastuzumab, and all-grade left ventricular ejection fraction decline/congestive heart failure for pazopanib and sunitinib; and all-grade corrected QT interval prolongation for vandetanib.

Conclusions: Our review provides an accessible summary of the cardiovascular toxicity of targeted therapy to assist clinicians and patients when managing cardiovascular health.