[2101] Mature cardiac safety results of dose-dense (DD) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) with trastuzumab (H) in HER2/neu overexpressed/amplified breast cancer (BCA).
Dang C, Smith K, Fornier M, Sugarman S, Troso T, Lake D, D'Andrea G, Seidman A, Sklarin N, George R, Dickler M, Currie V, Gilewski T, Moynahan ME, Drullinsky P, van Poznak C, Robson M, Wasserheit C, Mills N, Steingart R, Norton L, Hudis C.. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: With the superiority of DD q 2 weekly (w) AC 
T over conventionally scheduled (cs) AC T in CALGB 9741(Citron et al, JCO 2003, Hudis et al, SABCS 2005) and the known cardiac safety data of adjuvant H in NSABP B-31 (Geyer C et al, SABCS 2003, Romond et al, NEJM 2005), NCCTC N9831 (Perez et al, ASCO 2005), and HERA trial (Piccart-Gebhart et al, NEJM 2005), we are testing DD q 2 w AC T + H x one year as adjuvant treatment (Rx) of patients (pts) with HER2/neu (+) BCA to determine cardiac safety. Based on the reported cardiac event (CE) rate of < 4% in these trials in pts who received cs chemoRx + H, we planned this trial evaluating DD q 2 w AC T + H. The 1
endpoint is cardiac safety, defined as discontinuation of H due to 1) cardiac death or 2) symptomatic congestive heart failure (CHF). The 2 endpoint is time to recurrence and overall survival.
Methods: Pts w/ HER2/Neu IHC 3+ or FISH-amplified BCA were enrolled, regardless of tumor size or nodal status. Rx consisted of AC at 60/600 mg/m2 x 4 T at 175 mg/m2 x 4 q 2 w with pegfilgrastim 6 mg on day 2 + H x one year (H 4 mg/kg bolus and 2 mg/kg q w during T and 6 mg/kg q 3 w after all chemoRx is completed). A multi-gated radionuclide angiography scan (MUGA) is obtained at baseline and at months (mo) 2, 6, 9, and 18. Pts with baseline LVEF of > 55% and w/o cardiac illnesses as specified by the study are eligible. Pts with significant (sig) asymptomatic (asx) LVEF 
after DD AC based on mo 2 MUGA will not receive H, and pts w/ sig asx LVEF during H may have H held permanently, as per protocol.
Results: From January 4, 2005 to November 1, 2005, we enrolled all 70 planned pts. Median age was 49 years (range, 27-72). Forty one of 70 pts (60%) were node (+) and 27/70 pts (40%) were node (-). Median (med) baseline LVEF is 68% (range, 55%-81%). As of May 15, 2006, all pts had mo 2 MUGA after DD AC and there were no sig LVEF with a med LVEF of 67% (range, 58%-79%). So far 67 pts had mo 6 MUGA w/ med LVEF of 66% (range, 56%-75%); there were 3 pts w/ sig asx LVEF and came off study. Forty-one pts had mo 9 MUGA w/ a med LVEF of 65% (range, 57%-72%). One patient had CHF around mo 4 of Rx and came off study; pt is currently clinically well on cardiac medications.
Discussion: This is the 3rd report of cardiac safety of DD AC T + H. So far this Rx appears to be feasible w/ only one case of CHF (responding well to management) out of 70 treated pts at a med of 13 months of follow-up. Updated results will be presented.
Friday, December 15, 2006 7:00 AM
Poster Session II: Treatment: Adjuvant Therapy (7:00 AM-9:00 AM)