Cardiotoxicity in advanced HER2 positive breast cancer in real world Australian patients receiving HER2-targeted therapy in the first-line setting

Abstract

Aims and methods: The incidence and outcome of HER2-related cardiotoxicity is not well described in the routine care of patients with advanced HER2 positive breast cancer. We reviewed BioGrid's ©c 'Treatment of Advanced BreastCancer in the HER2 Positive Australian Patient' registry data to elucidate this problem further. Result(s):One hundred sixty-two female patients from seven Australian centres with a median age of 58.5 years (range 27-95) were included. Sixty-ninewomen(43%) had no risk factors for cardiotoxicity; 12 (18%) had at least two risk factors. Median baseline left ventricular ejection fraction (LVEF) was 64% (range 50-77). Of the 149 women who received HER2-targeted therapy, eight (6%) experienced cardiotoxicity (of any CTCAE left ventricular systolic dysfunction grade) in the first-line setting; five of which were asymptomatic. The median age (61 years) and baseline LVEF (60%, range 54-61) were similar to the whole cohort. However, only two of eight (25%) patients had no risk factors for cardiotoxicity, while three of eight (38%) had at least two risk factors. The onset of cardiotoxicity occurred at a median of 9 months (range 3.5-16.8) of treatment. In seven of two patients, HER2 therapy was withheld. Resolution of cardiotoxicity was seen in five of eight patients (median time to recovery 2.8 months (range 1.4-3.8). There was no difference between cardiotoxicity grade and resolution. Of the seven patients that had treatment withheld, only one resumed therapy. No patients died secondary to cardiotoxicity. Conclusion(s): The incidence of cardiotoxicity in our dataset is low compared to other retrospective reviews. While there may be underreporting, the results provide reassurance for clinicians, particularly when at least two risk factors are present, that HER2-targeted therapy can be safely administered and that where cardiotoxicity develops, it usually resolves with treatment discontinuation. The safety and ongoing management following re-challenge remains uncertain and requires investigation. Further research is required to under stand optimal patient selection for HER2 targeted therapy, cardiac monitoring, and cardiotoxicity management.