Five year update of cardiac dysfunction on NSABP B-31, a randomized trial of sequential doxorubicin/cyclophosphamide (AC)→paclitaxel (T) vs. AC→T with trastuzumab (H)

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LBA513 Background: Trastuzumab (H) has been shown to improve survival in HER2 positive, node-positive breast cancer patients when combined with paclitaxel following AC (Romond NEJM 2005:353;1673–1684). Cardiac dysfunction is the major toxicity associated with this regimen. Methods: NSABP B-31 compared doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel plus 52 weeks of trastuzumab beginning concurrently with paclitaxel in patients with node- positive, HER2-positive breast cancer. Initiation of trastuzumab required normal post-AC left ventricular ejection fraction (LVEF) on MUGA scan. If symptoms suggestive of congestive heart failure (CHF) developed, source documents were blindly reviewed by a panel of cardiologists to determine whether criteria were met for a cardiac event (CE), defined as NYHA class III or IV CHF or possible/probable cardiac death. Among patients with normal post-AC LVEF who began post-AC treatment, 10 of 872 (1.3%) control patients subsequently had confirmed CEs (9 CHFs and 1 cardiac death) compared with 35 of 932 (3.9%) trastuzumab-treated patients (35 CHFs and no cardiac deaths). The difference in cumulative incidence at 5 years was 2.7%. Risk factors for CHF were age 50 (5.2–5.3%), requirement for hypertension medication (7.7%), and post AC-LVEF values of 50–54% (13.0%). Conclusion: Administering trastuzumab with paclitaxel after AC increases incidence of CHF. Risk factors for increased risk of cardiotoxicity should be carefully considered when discussing benefits and risks of this therapy. No significant financial relationships to disclose.