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

• Published in: Cancer 2013-11, Vol.119 (22), p.3943-3951
• Main Authors: Morris, Patrick G., Iyengar, Neil M., Patil, Sujata, Chen, Carol, Abbruzzi, Alyson, Lehman, Robert, Steingart, Richard, Oeffinger, Kevin C., Lin, Nancy, Moy, Beverley, Come, Steven E., Winer, Eric P., Norton, Larry, Hudis, Clifford A., Dang, Chau T.
• Format: Article
• Language: English
• Subjects: Age; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - enzymology; Breast Neoplasms - pathology; cardiac safety; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Disease-Free Survival; dose‐dense chemotherapy; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; early breast cancer; efficacy; Female; Gynecology. Andrology. Obstetrics; Heart Failure - chemically induced; Humans; lapatinib; Mammary gland diseases; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Quinazolines - administration & dosage; Quinazolines - adverse effects; Receptor, ErbB-2 - biosynthesis; Retrospective Studies; Trastuzumab; Treatment Outcome; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.28284

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. Cancer 2013;119:3943–3951. © 2013 American Cancer Society. The authors conducted 2 consecutive phase 2 trials for early breast cancer that overexpresses human epidermal growth factor receptor‐2 (HER2) and concluded that, with up to 7 years of follow‐up, dose‐dense, anthracycline‐based chemotherapy can be safely combined with sequential anti‐HER2 therapy with acceptable cardiac toxicity. Furthermore, disease control rates in these studies appear to be encouraging.