Background: A previous feasibility trial (E2104 – Ann Oncol 23(2):331–7,2012) suggested incorporation of B into anthracycline-containing adjuvant therapy was feasible but ongoing cardiac monitoring was required to define the true impact of B on cardiac function.

Methods: Patients (pts) were assigned 1:2:2 to one of three treatment arms. In addition to doxorubicin and cyclophosphamide followed by weekly paclitaxel, patients received either placebo (Arm A – AC>T) or B during chemotherapy (Arm B - BAC>BT), or B during chemotherapy followed by B monotherapy (15 mg/kg q3wk) for an additional 10 cycles (Arm C – BAC>BT>B). Randomization was stratified and B dose adjusted for choice of AC schedule (classical q3wk − 15 mg/kg; dose dense(dd) q2 wk − 10 mg/kg). When indicated, radiation and hormonal therapy were administered concurrently with B (for Arm C pts). The primary cardiac endpoint was the incidence of clinically apparent cardiac dysfunction (CHF)defined as symptomatic decline in left ventricular ejection fraction (LVEF) to below the lower limit of normal (LLN) or symptomatic diastolic dysfunction as assessed by independent review. Cumulative toxicity data as of Jan 23, 2012 are presented.

Results: From 11.07 to 2.11, 4994 pts were enrolled. Median age was 52; 80% received ddAC. Chemotherapy associated toxicities including myelosuppression (Grade 4 neutropenia 16/20/19%) and neuropathy (Grade ≥ 3 8/8/8%) were similar across all arms. Grade ≥ 3 hypertension/thrombosis/proteinuria/hemorrhage was reported by 7/3/<1/<1% of B-treated pts. 99 pts developed CHF, most commonly reported at the post-AC or post-T evaluation. After a median follow-up of 26 months, the cumulative incidence of clinical CHF at 15 months from randomization in Arm A/B/C was 1.0/1.7/2.9% respectively. Median age of CHF pts was 57; median baseline LVEF of CHF pts was 60.

Conclusion: Incorporation of B into anthracycline and taxane containing adjuvant therapy results in a significant but small increase in clinical CHF. The rate of clinical CHF is similar to that predicted by E2104 (2.5–2.9%) and reported In the FDA label for anthracycline pre-treated pts(3.8%). No unexpected toxicities were encountered.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-17-01.