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|Patrick G|PG|', 'Iyengar|Neil M|NM|', 'Patil|Sujata|S|', 'Chen|Carol|C|', 'Abbruzzi|Alyson|A|', 'Lehman|Robert|R|', 'Steingart|Richard|R|', 'Oeffinger|Kevin C|KC|', 'Lin|Nancy|N|', 'Moy|Beverley|B|', 'Come|Steven E|SE|', 'Winer|Eric P|EP|', 'Norton|Larry|L|', 'Hudis|Clifford A|CA|', 'Dang|Chau T|CT|']
D061067:Antibodies, Monoclonal, Humanized D000971:Antineoplastic Combined Chemotherapy Protocols D001943:Breast Neoplasms D003520:Cyclophosphamide D018572:Disease-Free Survival D004317:Doxorubicin D005260:Female D006333:Heart Failure D006801:Humans D000077341:Lapatinib D008875:Middle Aged D017239:Paclitaxel D011799:Quinazolines D018719:Receptor, ErbB-2 D012189:Retrospective Studies D000068878:Trastuzumab D016896:Treatment Outcome
cardiac safety trastuzumab lapatinib early breast cancer dose-dense chemotherapy efficacy