Phase II feasibility trial incorporating bevacizumab into dose-dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node-positive breast cancer: A trial of the Eastern Cooperative Oncology Group (E2104).

520 Background: Little is known about the safety of combining bevacizumab and anthracyclines. Therefore, E2104 was a two-arm non-randomized phase II trial designed to evaluate the safety of incorporating bevacizumab into an anthracycline containing adjuvant therapy.,Patients (pts) were sequentially assigned to one of two treatment arms. In addition to dose dense doxorubicin and cyclophosphamide followed by paclitaxel (ddAC>T), all pts received bevacizumab (10 mg/kg q2 wks×26) either initiated concurrently with AC (Arm A: ddBAC>BT>B) or initiated concurrently with paclitaxel (Arm B: ddAC>BT>B). The primary endpoint was the incidence of clinically apparent cardiac dysfunction (CHF).,From October 2005 to November 2006, 226 pts were enrolled (Arm A 104, Arm B 122). Median age was 50 (range 27-76). Myelosuppression was common (G3/4 neutropenia 26%) but febrile neutropenia was rare (3%). G3 hypertension/thrombosis/proteinuria/hemorrhage was reported by 11/2/1/<1% of pts. respectively. One pt developed Grade 4 cerebrovascular ischemia. Median follow-up is 14.6 mos. for Arm A and 10.8 mos. for Arm B; to date 52 pts in Arm A and 8 in Arm B have completed planned therapy. Median pre-treatment LVEF was 65% in Arm A and 64% in Arm B. Clinical CHF was reported in 2 pts in Arm A after 4 and 6 cycles; four pts had asymptomatic declines in LVEF to <40% after 4 (n=1) and 16 cycles (n=3). Two pts in Arm B reported clinical CHF due to diastolic dysfunction (both associated with a decline in LVEF to 40-50%) after 4 and 9 cycles; one pt had asymptomatic decline in LVEF to <40% after 8 cycles.,Preliminary data suggests incorporation of bevacizumab into anthracycline-containing adjuvant therapy is feasible. Ongoing cardiac monitoring is required to define the true impact of bevacizumab on cardiac function. [Table: see text] [Table: see text].