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.
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.
Authors: Laura J Esserman; Donald A Berry; Angela DeMichele; Lisa Carey; Sarah E Davis; Meredith Buxton; Cliff Hudis; Joe W Gray; Charles Perou; Christina Yau; Chad Livasy; Helen Krontiras; Leslie Montgomery; Debasish Tripathy; Constance Lehman; Minetta C Liu; Olufunmilayo I Olopade; Hope S Rugo; John T Carpenter; Lynn Dressler; David Chhieng; Baljit Singh; Carolyn Mies; Joseph Rabban; Yunn-Yi Chen; Dilip Giri; Laura van 't Veer; Nola Hylton Journal: J Clin Oncol Date: 2012-05-29 Impact factor: 44.544
Authors: Paul Gaß; Peter A Fasching; Tanja Fehm; Johann de Waal; Mahdi Rezai; Bernd Baier; Gerold Baake; Hans-Christian Kolberg; Martin Guggenberger; Mathias Warm; Nadia Harbeck; Rachel Wuerstlein; Jörg-Uwe Deuker; Peter Dall; Barbara Richter; Grischa Wachsmann; Cosima Brucker; Jan W Siebers; Nikos Fersis; Thomas Kuhn; Christopher Wolf; Hans-Walter Vollert; Georg-Peter Breitbach; Wolfgang Janni; Robert Landthaler; Andreas Kohls; Daniela Rezek; Thomas Noesselt; Gunnar Fischer; Stephan Henschen; Thomas Praetz; Volker Heyl; Thorsten Kühn; Thomas Krauss; Christoph Thomssen; Andre Hohn; Hans Tesch; Christoph Mundhenke; Alexander Hein; Claudia Rauh; Christian M Bayer; Adib Jacob; Katja Schmidt; Erik Belleville; Peyman Hadji; Sara Y Brucker; Matthias W Beckmann; Diethelm Wallwiener; Sherko Kümmel; Christian R Löhberg Journal: Breast Care (Basel) Date: 2016-10-27 Impact factor: 2.860
Authors: Robert Wesolowski; Mahmoud Abdel-Rasoul; Maryam Lustberg; Maria Paskell; Charles L Shapiro; Erin R Macrae Journal: Oncologist Date: 2014-05-02