期刊
ANNALS OF ONCOLOGY
卷 22, 期 2, 页码 301-306出版社
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdq350
关键词
bevacizumab; breast cancer; everolimus; lapatinib; neoadjuvant; trastuzumab
类别
资金
- Roche
- Sanofi-Aventis
- GlaxoSmithKline
- Novartis
Background: Safety data for combining bevacizumab, everolimus, or lapatinib with anthracycline-and taxane-based neoadjuvant chemotherapy for breast cancer are limited. Patients and methods: The neoadjuvant GeparQuinto trial investigates the addition of (i) bevacizumab to four cycles epirubicin/cyclophosphamide (EC) followed by four cycles docetaxel (Taxotere) in patients with human epithelial growth factor receptor (HER)2-negative tumors, (ii) everolimus to weekly paclitaxel in patients with HER2-negative tumors not responding to EC +/- bevacizumab, and (iii) lapatinib instead of trastuzumab to EC-docetaxel in patients with HER2-positive tumors to improve the rate of pathological complete response. Tolerable dose, need for supportive treatments, and early signals for toxic effect were evaluated in a planned safety analysis of 270 patients. Results: Treatment with chemotherapy plus bevacizumab, everolimus, or lapatinib was discontinued in 23.0%, 25.8%, and 34.5% compared with chemotherapy alone or plus trastuzumab in 19.4%, 24.1%, 3.2%, respectively. More leukopenia, infections, mucositis, and hypertension but less edema was observed by adding bevacizumab; a trend toward more thrombocytopenia, leukopenia, skin changes, and hyperlipidemia by adding everolimus; and more diarrhea, skin changes, and hot flushes but no cardiac events by substituting trastuzumab by lapatinib. Conclusions: Adding bevacizumab and everolimus to chemotherapy appeared feasible. Lapatinib at 1250 mg resulted in an increased rate of treatment discontinuations and was subsequently dose reduced to 1000 mg.
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