Review

Cardiac surveillance for anti-HER2 chemotherapy

Patrick Collier, MD, PhD, FASE, FESC, FACC, Muzna Hussain, MD, Zoran B. Popovic, MD, PhD and Brian P. Griffin, MD
Cleveland Clinic Journal of Medicine February 2021, 88 (2) 110-116; DOI: https://doi.org/10.3949/ccjm.88a.19150

Article Figures & Data

Tables

  • TABLE 1

    Trials involving anti-HER2 treatment

    Studya YearNo. of patientsDuration (years)Early vs metastaticAnthracyclineFollow-up (years)Echocardiography resultLVEF drop (%)Heart failure incidence (%)Cardiac death (%)
    OHERA7 20193,7331EarlyYes54+23< 1
    KATHERINE8 20191,4860.4EarlyNo54+NANA0
    NSABP9 20174071EarlyYes54+1NA< 1
    HERA10 20175,0991–2EarlyNo104+< 1NANA
    APHINITY11 20174,8051EarlyNo105+NA< 1< 1
    Dang et al12 20164061BothNo44+3< 1NA
    HORG13 20154811EarlyNo73+< 100
    CLEOPATRA14 20138041BothNo33+1< 1< 1
    NeoSphere15 20124170.4BothNo2 weeks3+< 1< 10
    BCIRG-00616 20113,2221BothYes57+14< 10
    Slamon et al6,b 20012340.8MetastaticYes> 2NA16270

    • ↵a All trials included radiation therapy and were adjudicated.

    • ↵b Pivotal trial leading to stringent US Food and Drug Administration recommendations for cardiac surveillance.

    • APHINITY = A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 (HER2)-Positive Primary Breast Cancer; BCIRG = Breast Cancer International Research Group; CLEOPATRA = A Study to Evaluate Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer; HER2 = human epidermal growth factor receptor 2; HERA = HERceptin Adjuvant; HORG = Hellenic Oncology Research Group; KATHERINE = A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy; LVEF = left ventricular ejection fraction; NA = not available; NeoSphere = A Study of Pertuzumab in Combination With Herceptin in Patients With HER2 Positive Breast Cancer; NSABP = National Surgical Adjuvant Breast and Bowel Project; OHERA = Observational Study of Cardiac Events in Patients with HER2-Positive EBC Treated with Herceptin

  • TABLE 2

    Wilson’s criteria for an ideal screening test, applied to cardiac surveillance for chemotherapy

    Criteria24Surveillance echocardiography for chemotherapy
    The condition should be an important health problemCardiotoxicity is an important health problem but is detectable by screening only in a minority of patients
    The natural history of the condition should be understoodThe natural history of cardiotoxicity has been reasonably well studied for established chemotherapy agents such as anti-HER2
    There should be a recognizable latent or early symptomatic stageLeft ventricular dysfunction typically relates to acute toxicity and becomes manifest within the first year of exposure. Early recognition is important, because cumulative doses typically compound toxicity
    A test should exist that is easy to perform and interpret, and is acceptable, accurate, reliable, sensitive, and specificImaging with echocardiography has these qualities but also involves considerable challenges and limitations
    An accepted treatment for the disease should existCurrent guideline-directed heart failure management is recognized as treatment for chemotherapy-related cardiomyopathy. Evidence is limited for specific treatments beyond these guidelines, although the subject is under active investigation
    Treatment should be more effective if started earlyIf started early, current guideline-directed heart failure management is considered to be more effective. Early recognition of chemotherapy-related cardiomyopathy is important for preventing additional dose exposures, which typically compound toxicity
    There should be a policy on who should be treatedCurrent guideline-directed heart failure management covers who should be treated
    Diagnosis and treatment should be cost-effectiveLimited data suggest favorable cost-effectiveness for screening and early treatment, although a more targeted approach can likely significantly improve it
    Case-finding should be a continuous processCase-finding can be a continuous process
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