More Awareness Needed of Heart Events Tied to Breast Cancer Drugs, Experts Say

Derick Alison
Derick Alison
7 Min Read

Pharmacovigilance is needed to identify, monitor, and prevent cardiovascular adverse events (CV-AEs) associated with new agents for breast cancer and to reduce the risk of cardiotoxicity for the growing number of survivors, according to experts.

Adverse events such as cardiovascular toxicities must be considered “in light of effectiveness of recently approved drugs” for breast cancer treatment, including elacestrant (Orserdu), tucatinib (Tukysa), neratinib (Nerlynx), olaparib (Lynparza), immune checkpoint inhibitors (ICIs), trastuzumab deruxtecan (Enhertu), and sacituzumab govitecan (Trodelvy), noted Lisa Anne Carey, MD, ScM, of the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill, and co-authors.

“It is important to recognize, treat, and control pre-existing cardiovascular risk factors before initiating cardiotoxic drugs,” the authors wrote in JCO Oncology Practice. “Identification of cardiotoxicity can change clinical outcome, reducing mortality and complications. In this context, the new field of cardio-oncology aims to prevent, monitor, and treat CV-AEs.”

This will improve “awareness that many of the drugs we currently use, which have expanded massively in the past few years, have cardiac and vascular implications,” Carey told MedPage Today. “There is an increasing role for co-management with our cardiology colleagues.”

In an accompanying editorial, Rohit Moudgil, MD, PhD, and colleagues from the Cleveland Clinic Foundation, agreed, emphasizing that clinicians should be “on the lookout” for CV-AEs related to breast cancer treatment. “Pharmacovigilance is an ongoing process and should be part of our daily clinical practice,” they wrote.

The review showed that while anti-HER2 agents have transformed prognosis for the 25% of breast cancer patients with HER2-positive disease, the incidence of decreased left ventricular ejection fraction (LVEF) associated with trastuzumab (Herceptin) ranged from 4% to 27%. The associated risk was highest when the anti-HER2 monoclonal antibody was used in combination with anthracyclines, the authors noted, which includes agents such as doxorubicin (Adriamycin) and epirubicin (Ellence).

Notably, the true incidence of cardiotoxicity associated with breast cancer agents may be higher than what is indicated by clinical trial data. In an analysis of adverse event data from the monarchE study, thrombosis rates of 1% to 5% were reported with the use of cyclin-dependent kinase (CDK) 4 and 6 inhibitors in high-risk early breast cancer, but real-world data have shown CDK4/6 inhibitor-related thrombosis rates of 9.8%.

Venous thromboembolism (VTE) has been observed with the use of the CDK4/6 inhibitors palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio). An increased relative risk of 2.62 for VTE with all three was seen compared with endocrine therapy alone, particularly when paired with tamoxifen.

Tamoxifen has been shown to be associated with venous thrombosis and VTE, and should not be used in patients with a history of deep vein thrombosis, pulmonary embolism, or those who require anticoagulant therapy. On the other hand, aromatase inhibitors are associated with a higher risk of hypertension, hyperlipidemia, and arrhythmia, but a significantly lower risk of thrombosis, compared with tamoxifen.

The editorialists reported observing a 16% incidence of atrial fibrillation (AF) in patients treated with ibrutinib (Imbruvica), though they also pointed to a 2018 study that reported a 0.5% incidence of ibrutinib-associated AF.

The review authors also noted that paclitaxel-related cardiotoxicity can manifest as arrhythmias, particularly sinus bradycardia, while lymphedema is the most common docetaxel-related vascular AE.

Approaches to the prevention or treatment of cardiotoxicity, especially with anthracyclines or anti-HER2 agents, have been met with mixed results, the review showed. Results from the phase III MANTICORE-101 Breast trial showed that in patients with HER2-positive breast cancer receiving trastuzumab after anthracyclines, angiotensin-converting enzyme (ACE) inhibitors and beta-blockers were not effective in preventing left ventricular remodeling.

Immune-related CV-AEs or isolated elevated cardiac biomarkers associated with the use of trastuzumab deruxtecan and sacituzumab govitecan — including myocarditis, dysrhythmias, congestive heart failure, vasculitis, and pericarditis — require prompt attention. High-dose corticosteroids may be needed to treat ICI-induced CV-AEs, and when refractory, other immunosuppressive drugs such as alemtuzumab (Campath) or abatacept (Orencia) may be used.

Close monitoring of symptoms and signs is recommended during treatment with a cardiotoxic agent. “Along with LVEF assessment and consideration of cardiac biomarkers, a more sensitive echocardiography assessment, global longitudinal strain, may identify areas of myocardial and contractile function damage not otherwise detectable,” Carey and colleagues wrote, noting that the approach is not standard. “Once a CV-AE is detected, timely discontinuation of the offending agent is crucial, and all clinical manifestations need to be managed.”

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    Kristin Jenkins has been a regular contributor to MedPage Today and a columnist for Reading Room, since 2015.

Disclosures

This review was funded by the National Cancer Institute Breast SPORE program, the Susan G Komen and International Breast Cancer Research Foundation, the Ermenegildo Zegna scholarship, and Fondazione IEO-Monzino.

Carey reported relationships with NanoString Technologies, Seagen, Veracyte, AstraZeneca, Gilead Sciences, Novartis, Lilly, Genentech/Roche, and GSK. Co-authors also reported multiple relationships with industry.

The editorialists reported no conflicts of interest.

Primary Source

JCO Oncology Practice

Source Reference: Zagami P, et al “Cardiotoxicity of agents used in patients with breast cancer” JCO Oncol Pract 2023; DOI: 10.1200/OP.23.00494.

Secondary Source

JCO Oncology Practice

Source Reference: Abdallah K, et al “Breast cancer therapies: a cardiac perspective” JCO Oncol Pract 2023; DOI: 10.1200/OP.23.00665.

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