Cardiac Safety Results of a Phase II Trial of Adjuvant Docetaxel/Cyclophosphamide Plus Trastuzumab (Her TC) in HER2+ Early Stage Breast Cancer Patients.

Background: Docetaxel/cyclophosphamide (TC) has superior activity to doxorubicin/cyclophosphamide (AC) in the adjuvant treatment of patients (pts) with early breast cancer and is devoid of known cardiac toxicity (Jones et al, JCO 27:1177-1183, 2009). Although the addition of trastuzumab (H) to anthracycline-based adjuvant regimens is effective, it is associated with increased cardiac toxicity. Therefore, a short course of the nonanthracycline TC regimen coupled with H appeared to be a logical combination for women with lower risk HER2+ breast cancer. We report the cardiac safety of the TC+H regimen for the first group of women to complete 1 year of treatment. Patients and Methods: 263 pts were registered to the study and stratified by nodal status (positive/negative). Pts must have had baseline left ventricular ejection fraction (LVEF) ≥50% by MUGA or ECHO. On Day 1 of each 21-day cycle for a total of 4 cycles, pts received: (T) 75 mg/m 2 IV, followed by (C) 600 mg/m 2 IV. Weekly (H) was also given at 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV Days 1, 8, 15 thereafter throughout chemotherapy. After completion of chemotherapy, H was administered at 6 mg/kg IV every 3 weeks to complete 12 months of therapy with H. Decreased LVEF was defined as a decrease from baseline (start of treatment) to completion of TC+H, or when assessed at 3-month intervals until the completion of H treatment. H was withheld if there was a 15% or more decline in LVEF (absolute %). Treatment was discontinued after 2 or 3 treatment delays at investigator9s discretion (same rules as prior studies). This report focuses on cardiac safety occurring during the 3 months of chemotherapy plus 1 year of H therapy. Results: To date, 260 pts completed 1 year of treatment and comprised the cardiac safety population; median age was 55 yrs (30-76); 90% of pts had ECOG 0; 64% were ER+, 47% were PR+, and 77% had no lymph node involvement. 184 pts (70%) completed planned treatment and 23 pts (9%) discontinued treatment due to adverse events. A total of 61 pts (23.5%) had declines of ≥10% LVEF; 8 pts (3.1%) had 2 or more LVEF declines ≥10% and were taken off treatment before 1 year of H was completed, and 16 pts (6.1%) had declines of LVEF below 50% during treatment. No patient had clinical CHF. Conclusions: H combined with 4 cycles of the nonanthracycline TC regimen produced a low rate of cardiac events, mainly asymptomatic drops in LVEF, but no reported cases of CHF. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5082.