Audit on incidence of Trastuzumab induced Cardiac toxicity in day care Oncology at a tertiary care hospital, Karachi, Pakistan

Transtuzumab induced cardiotoxicity is generally reversible and can usually be managed with medical treatment. Cardiac function is improved both in patients who continue trastuzumab and in those in whom further therapy is withdrawn, indicating that with careful cardiac management by cardiologist, anticancer therapy can be continued. It is generally accepted that, unlike anthracyclines, the cardiotoxicity caused by trastuzumab is not dose-dependent, does not occur in all patients, and is reversible. ⁽¹⁾

It is important in the management of both early and advanced disease. It improves survival in advanced breast cancer patients. Symptomatic heart failure is the adverse effect caused by this antibody seen in intravenous trastuzumab infusion ^(2). The most common immediate side effects seen in treatment of metastatic breast cancer with intravenous trastuzumab are fever, chills, headache, infection, congestive heart failure, insomnia, cough, and rash. women who are pregnant or planning to get pregnant should not take trastuzumab because it can harm the developing foetus ⁽³⁾

It usually manifests in the form of asymptomatic decrease in left ventricular ejection fraction. Echocardiogram is the tool to monitor ejection fraction in patients receiving this antibody at every three months. Serious and fatal drug reactions have been reported with intravenous trastuzumab therapy. ⁽⁴⁾

Trastuzumab is a subcutaneous formulation that contains hyaluronidase, which temporarily and reversibly degrades hyaluronan, a gel-like substance that forms a barrier between cells under the skin. This enables the subcutaneous formulation of trastuzumab to be rapidly dispersed and absorbed over a greater area. ⁽⁵⁾

Trastuzumab subcutaneous is approved in combination with chemotherapy for the adjuvant (post-surgery) treatment of HER2-positive early breast cancer and first-line treatment of advanced HER2-positive breast cancer.

In addition to left ventricular dysfunction and heart failure, studies also reported the development of arrhythmias, sick sinus node syndrome, and atrial flutter in patients undergoing treatment with trastuzumab. ⁽⁶⁾ Recently, through a secondary analysis of a clinical trial, investigators found that trastuzumab induced hypertension is characterized by the presence of both left ventricular dysfunction and reversible myocardial inflammation and edema, and that trastuzumab may be associated with harmful changes in cardiac metabolic phenotype.⁽⁶⁾

Improvement in cardiac function is seen both in patients who continue trastuzumab and in those in whom further therapy is withdrawn, indicating that with careful management trastuzumab therapy can be continued, it is generally accepted that, unlike anthracyclines, the cardiotoxicity caused by trastuzumab is not dose-dependent, does not occur in all patients, and is reversible. ⁽⁷⁾

A frequently used definition of treatment-related cardiotoxicity in clinical trials is an absolute decrease in left ventricular ejection fraction (LVEF) of 10% to a value of <55%

Researchers analysed 1,437 echocardiograms from 324 patients over a follow-up period of up to 3.5 years and revealed three main patterns of Left ventricular ejection fraction (LVEF) slow decline with time mild early and late sustained decline, early significant decline with late partial recovery. ^(8-9)