St. Gallen breast cancer meeting in Switzerland reconfirms herceptin cardiotoxicity

[Lani]

on the whole reversible( data from the HERA study):

Trastuzumab-Associated Cardiotoxicity Mostly Reversible: Presented at SGOC [Doctor's Guide]
ST. GALLEN, SWITZERLAND — March 19, 2007 — The cardiac side effects associated with use of the breast cancer drug trastuzumab appear to be reversible, new data from the landmark HERceptin Adjuvant (HERA) study indicate.

Trastuzumab is a humanised antibody that targets human epidermal growth factor receptor 2 (HER2), a protein that is overexpressed in 20% to 30% of breast cancers and is associated with a particularly aggressive form of the disease.

When given after adjuvant chemotherapy, trastuzumab has been shown in several large studies to significantly improve disease-free and overall survival in women with HER2-positive breast cancer.

Although trastuzumab is well tolerated overall, however, there are concerns over the drug's potential to cause cardiotoxicity. In particular, trastuzumab therapy is associated with an increased risk of congestive heart failure (CHF).

To better understand these effects, the HERA trial incorporated a safety substudy in which 3,386 participants underwent detailed cardiac monitoring at baseline, 3, 6, 12, 24, 30, 36, and 60 months.

Results: from the first 12 months of follow up were presented in a poster session here at the 10th International St. Gallen Oncology Conference (SGOC): Primary Therapy of Early Breast Cancer, held in St. Gallen, Switzerland.

[Hopeful]

All subjects had normal left ventricular ejection fraction (LVEF greater than or equal to 55%) before starting trastuzumab therapy, according to study investigator Thomas Suter, MD, chief, inpatient services, department of cardiology, Swiss Cardiovascular Centre, University of Berne, University Hospital, Inselspital, Berne, Switzerland.

Overall, 4.3% of trastuzumab-treated patients discontinued therapy due to cardiac disorders. Rates of cardiac dysfunction (3.04% vs 0.53%), symptomatic CHF (2.15% vs 0.12%), and severe CHF (0.60% vs 0%) were all significantly higher in the trastuzumab arm compared with the observation arm.

There were no cardiac deaths in the trastuzumab arm, however, versus 1 in the observation arm.

Importantly, most patients who experienced a cardiac event had a recovered LVEF after a median of 189 days. This was also true among patients who developed severe CHF, of whom 80% were asymptomatic and 60% had a recovered LVEF after a median of 124 days.

More detailed analysis revealed a number of risk factors for cardiac endpoints, the researchers reported. Variables associated with a significantly increased risk included a lower LVEF at baseline, body mass index >25 m<SUP>2</SUP>. In addition, the cumulative dose of doxorubicin or epirubicin chemotherapy received was significantly higher among patients who experienced cardiotoxicity versus those who did not.

The researchers say that the considerable reduction in the risk of cancer recurrence with trastuzumab outweighs the low cumulative incidence of cardiotoxicity, including cardiac death and CHF.

"In the HERA trial, there was a low incidence of cardiac endpoints after a median follow-up of 12 months," they concluded. "Results suggest that cardiac dysfunction is mostly reversible within this observation period but longer follow up is needed."


[Presentation title: Cardiac Side Effects in the Herceptin Adjuvant (HERA) Trial. Abstract P110]
Hopeful

[suzan w]

This is a very interesting article...thanks! Everything I have read/researched about herceptin says that the cardiotoxicity is reversed upon discontinuation of the drug...and that it has no lasting effects once treatment is completed...I think I have that right!!!

[Christine MH-UK]

A good result for HERA, but didn't Slamon find some longer term problems with the AC->(herceptin+taxotere)->year of herceptin arm of BCIRG006 that he thought might not be reversible? That is one of the reasons he has argued that Herceptin + carboplatin + taxotere -> rest of year on herceptin treatment is preferable.