Long-term cardiac safety and outcomes of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab with and without lapatinib in patients with early breast cancer.
BACKGROUND: The authors have previously reported 2 consecutive phase 2 trials in patients with early breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2) to assess the feasibility of incorporating anti-HER2 therapies into dose-dense (dd) chemotherapy regimens. The incidence of congestive heart failure (CHF) at a median follow-up of 2 years was 1.4% and 3.2%, respectively. METHODS: In trial A, patients received dd doxorubicin and cyclophosphamide (AC)→paclitaxel (T) (each given every 2 weeks) × 4 with trastuzumab (H) given × 1 year. In trial B, weekly T (weekly × 12) was substituted for ddT and lapatinib × 1 year was added. Herein, the authors report the longer-term incidence of CHF and distant disease-free survival (DDFS). RESULTS: From January 2005 to May 2008, 165 patients enrolled (median age, 46 years, with a median left ventricular ejection fraction of 68% [range, 52%-81%]), 17%of whom had previous hypertension. With a median follow-up of 84 months (trial A) and 57 months (trial B), 1 additional patient developed CHF. Therefore, the cumulative incidence of CHF was 1.4% (95% confidence interval [95% CI], 1.36%-7.7%) for trial A and 4.2% (95% CI, 4.2%-10.4%) for trial B. The 5-year DDFS for trials A and B was 92% (95% CI, 83%-97%) and 89% (95% CI, 81%-94%), respectively. CONCLUSIONS: Longer follow-up of these 2 studies has demonstrated that ddAC→TH only or with lapatinib is associated with a low risk of CHF and promising DDFS in patients with early breast cancer.
Morris, PG; Iyengar, NM; Patil, S; Chen, C; Abbruzzi, A; Lehman, R; Steingart, R; Oeffinger, KC; Lin, N; Moy, B; Come, SE; Winer, EP; Norton, L; Hudis, CA; Dang, CT
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