Integrating bevacizumab, everolimus, and lapatinib into current neoadjuvant chemotherapy regimen for primary breast cancer. Safety results of the GeparQuinto trial.

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.