Left Ventricular Dysfunction

Management of left ventricular ejection fraction (LVEF) decrease with ENHERTU

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.
  • Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated
  • Manage LVEF decrease through treatment interruption
  • Permanently discontinue ENHERTU if LVEF of <40% or absolute decrease from baseline of >20% is confirmed

Dose modifications for decreased LVEF1

Severity Treatment Modification
LVEF greater than 45% and absolute decrease from baseline is 10% to 20%
  • Continue treatment with ENHERTU
LVEF 40% to 45% And absolute decrease from baseline is less than 10%
  • Continue treatment with ENHERTU
  • Repeat LVEF assessment within 3 weeks
And absolute decrease from baseline is 10% to 20%
  • Interrupt ENHERTU
  • Repeat LVEF assessment within 3 weeks
  • If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU
  • If LVEF recovers to within 10% of baseline, resume treatment with ENHERTU at the same dose
LVEF less than 40% or absolute decrease from baseline is greater than 20%
  • Interrupt ENHERTU
  • Repeat LVEF assessment within 3 weeks
  • If LVEF of less than 40% or absolute decrease from baseline of greater than 20% is confirmed, permanently discontinue ENHERTU
Symptomatic congestive heart failure (CHF)
  • Permanently discontinue ENHERTU
Toxicity grades are in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v.4.03).

Review information for these other potential treatment risks:

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