Trastuzumab-induced cardiac dysfunction: What happens when patients are rechallenged with the drug?

Objectives Reported rates of Trastuzumab –induced cardiac dysfunction (Tras-icd) have been variable but most investigations have shown reversibility upon discontinuation in the majority of cases. However data is scarce on the cardiac response of patients who recover, when they are rechallenged with the drug. Our objective was to establish the incidence of tras-icd in our population, confirm reversibility and evaluate cardiac response upon resumption of therapy.

Methods Retrospective study of all patients (n=93) with breast cancer who were monitored by serial equilibrium radionuclide ventriculography (ERNV) before and after initiation of Tras. Pts were excluded if they received other concomitant cardiotoxic chemotherapy (cc) such as anthracyclines. However 70 pts (75%) had undergone prior therapy with cc. We defined Tras-icd as a decline in LVEF of at least 10% to below 55% with or without accompanying signs or symptoms.

Results Of 93 pts, 18 had Tras-icd (19.3%). In most cases, the decline in LVEF was asymptomatic (17/18 or 94%). If Tras-icd was defined as decline of at least 10% to below 50%, 11 pts would qualify or 11.8%. In all pts with Tras-icd, the drug was discontinued and serial ERNV was performed. LVEF returned to baseline levels in 17/18 or 94%. Treatment with Tras was resumed in 15/17 pts and they were monitored with ERNV. Normal LVEF was maintained despite therapy in 13/15 (86%) and declined significantly in 2, (14%) requiring a second interruption.

Conclusions In our population, Tras-icd is most often asymptomatic and reversible and occurs in 11 to 19 % of pts, depending on the preset definition. When pts recover and are rechallenged with the drug, the majority (86%) maintains a normal LVEF.