Continuous Trastuzumab Therapy in Breast Cancer Patients With Asymptomatic Left Ventricular Dysfunction

Yu, Anthony F.; Yadav, Nandini; Eaton, Anne; Lung, Betty Y; Thaler, Howard T.; Liu, Jennifer E.; Hudis, Clifford A.; Dang, Chau T.; Steingart, Richard M.

doi:10.1634/theoncologist.2015-0125

Cited by 26 publications

(23 citation statements)

References 37 publications

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“…However, more recently, a retrospective review reported worsening in cardiac dysfunction in patients who were continued on trastuzumab therapy despite evidence of mild LVD during screening by transthoracic echocardiography (LVEF >50%). 162 The authors recommend considering continuing to treat patients with trastuzumab despite mild asymptomatic LVD by first starting cardioprotective therapy without withholding trastuzumab. 163 Asymptomatic patients with normal LVEF but decrease in average GLS.…”

Section: Asymptomatic New Laboratory Abnormalities (Or Preclinical Tmentioning

confidence: 99%

Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations

et al. 2020

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Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short-and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.

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Section: Asymptomatic New Laboratory Abnormalities (Or Preclinical Tmentioning

confidence: 99%

Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations

et al. 2020

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“…This is consistent with a previous study showing the tolerability of uninterrupted trastuzumab among patients who developed significant LVEF decline but remained greater than or equal to 50%. [15] Moving forward, it is important to determine the safety of continuing anti-HER2 therapy in patients with significant asymptomatic LVEF decline with LVEF of < 50%. Notably, SAFE-HEaRt is one such study which is a prospective clinical trial that is evaluating the cardiac safety of continuous trastuzumab, ado trastuzumab, or pertuzumab for patients with LVEF decline between 40% and 49% (NCT01904903).…”

Section: Discussionmentioning

confidence: 99%

“…Although less frequent cardiac monitoring could result in missed cases of asymptomatic LVEF decline, preliminary data suggest that continued trastuzumab may be well tolerated in this setting. [15] Additionally, it is still unclear on the long-term clinical significance of asymptomatic LVEF decline in the oncology setting. Limited cardiac monitoring, however, would minimize interruption of life-saving trastuzumab-based therapy and decrease healthcare costs by reducing unnecessary medical testing.…”

Section: Discussionmentioning

confidence: 99%

Cardiac safety of non-anthracycline trastuzumab-based therapy for HER2-positive breast cancer

Mukku

Verma

et al. 2017

Breast Cancer Res Treat

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Purpose Trastuzumab improves overall survival for women with HER2-positive breast cancer but is associated with cardiotoxicity, especially when administered after anthracyclines. Use of non-anthracycline trastuzumab-based regimens is rising, particularly for patients with low risk disease or with multiple cardiovascular risk factors. We performed a single center retrospective cohort study to assess the cardiac safety of trastuzumab without anthracyclines outside of a clinical trial setting. Methods A retrospective chart review was conducted of patients with HER2-positive early-stage breast cancer receiving non-anthracycline trastuzumab-based therapy between January 2010 and June 2014. Cardiovascular risk factors, left ventricular ejection fraction (LVEF), and treatment interruption data were collected. The primary outcome was a cardiac event (CE), defined by New York Heart Association class III or IV heart failure or cardiac death. The secondary outcome was a significant asymptomatic decline of LVEF (≥ 10% to < 55% or ≥ 16% from baseline). Results A total of 165 patients were identified with a median age of 59 years (range, 32 to 85 years). Seventy (42%) had hypertension, 52 (32%) had hyperlipidemia, 29 (18%) had diabetes, and 5 (3%) had coronary artery disease. All patients had a LVEF ≥ 50% (median, 67%; range, 50% to 80%) at baseline. Two (1.2%) patients with multiple cardiovascular risk factors developed a CE. After discontinuation of trastuzumab, both patients had recovery of LVEF to > 50% and resolution of heart failure symptoms. Ten (6.1%) patients developed significant asymptomatic LVEF decline during trastuzumab therapy. Conclusions The overall incidence of symptomatic heart failure and asymptomatic LVEF decline among patients receiving trastuzumab without anthracyclines remains low. These findings suggest that less intensive cardiac monitoring may be appropriate during trastuzumab therapy without anthracyclines.

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“…There is evidence that continuation of trastuzumab therapy, in combination with intensive administration of cardiac medication and close clinical surveillance for progressive left ventricular deterioration, may be a safe alternative to stopping trastuzumab in patients with mild, asymptomatic LV dysfunction. Retrospective data showed that when trastuzumab was continued without interruption in 31 patients with trastuzumab‐induced cardiotoxicity, no patients developed heart failure . Furthermore, we have published our experience evaluating the safety of continuing trastuzumab in patients despite mild, asymptomatic left ventricular impairment while being treated with ACE‐I and/or beta blockers in a cardio‐oncology clinic .…”

Section: There Is Scant Evidence To Inform the Optimal Approach To Trmentioning

confidence: 99%

Adjuvant Trastuzumab Therapy: Can We Balance Efficacy and Safety?

et al. 2019

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Trastuzumab is an effective treatment for HER2‐positive breast cancer. Current guidelines recommend withholding trastuzumab in patients experiencing a significant asymptomatic decline in left ventricular function. In this commentary, we discuss the survival benefits afforded by trastuzumab juxtaposed against the risk of trastuzumab‐mediated cardiotoxicity. It is not known whether the net benefit of continuing trastuzumab in the setting of mild cardiotoxicity outweighs the associated risks. We describe a potential approach undertaken by our group, and others, and call for a randomized trial.

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Continuous Trastuzumab Therapy in Breast Cancer Patients With Asymptomatic Left Ventricular Dysfunction

Cited by 26 publications

References 37 publications

Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations

Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations

Cardiac safety of non-anthracycline trastuzumab-based therapy for HER2-positive breast cancer

Adjuvant Trastuzumab Therapy: Can We Balance Efficacy and Safety?

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