Trastuzumab-related cardiotoxicity in the herceptin adjuvant trial

The updated analysis of cardiac adverse effects in the Herceptin Adjuvant (HERA) trial provides convincing evidence that the administration of trastuzumab sequentially after adjuvant chemotherapy and/or radiation therapy is safe.1 Not only was the rate of symptomatic congestive heart failure (CHF) quite low, but only 4.3% of the patients needed permanent trastuzumab discontinuation on account of cardiotoxicity, either symptomatic or asymptomatic. The incidence of cardiac events in the HERA trial compares favorably with that observed in the two North American trials, where trastuzumab was administered concomitantly with paclitaxel and on completion of four cycles of AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2).2 The rate of symptomatic congestiveCHF was approximately 4% but most importantly, because of protocol criteria, approximately 25% of the patients in the North American trials were not able to receive the intended treatment with trastuzumab, either on account of a significant drop in the left ventricular ejection fraction (LVEF) after AC (6.7%), or because of cardiac toxicity occurring during trastuzumab treatment (18.9%). Therefore, beyond the efficacy data, the sequential strategy has become popular also because it appears to be the safest when cardiac toxicity is concerned. One obvious critical question at this point is whether the cardiac safety of trastuzumab reported by the HERA investigators will be reproduced in the general population of patients treated outside clinical trials by the same sequential approach............