Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto)+.

von Minckwitz G, Loibl S, Untch M, Eidtmann H, Rezai M, Fasching P, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Huober J, Solbach C, Jackisch C, Kunz G, Blohmer J, Hauschild M, Fehm T, Nekljudova V, Gerber B, Gnauert K, Heinrich B, Pratz T, Groh U, Tanzer H, Villena C, Tulusan A, Liedtke B, Blohmer U, Kittel K, Mau C, Potenberg J, Schilling J, Just M, Weiss E, Buckner U, Wolfgarten M, Lorenz R, Doering G, Feidicker S, Krabisch P, Deichert U, Augustin D, Kunz G, Kast K, von Minckwitz G, Nestle-Kramling C, Rezai M, Hos C, Terhaag J, Fasching P, Staib P, Aktas B, Kuhn T, Khandan F, Mobus V, Solbach C, Tesch H, Stickeler E, Heinrich G, Wagner H, Abdallah A, Dewitz T, Emons G, Belau A, Rethwisch V, Lantzsch T, Thomssen C, Mattner U, Nugent A, Muller V, Noesselt T, Holms F, Muller T, Deuker J, Schrader I, Strumberg D, Uleer C, Solomayer E, Runnebaum I, Link H, Tome O, Ulmer H, Conrad B, Feisel-Schwickardi G, Eidtmann H, Schumacher C, Steinmetz T, Bauerfeind I, Kremers S, Langanke D, Kullmer U, Ober A, Fischer D, Kohls A, Weikel W, Bischoff J, Freese K, Schmidt M, Wiest W, Sutterlin M, Dietrich M, Grieshammer M, Burgmann D, Hanusch C, Rack B, Salat C, Sattler D, Tio J, von Abel E, Christensen B, Burkamp U, Kohne C, Meinerz W, Grashoff S, Decker T, Overkamp F, Thalmann I, Sallmann A, Beck T, Reimer T, Bartzke G, Deryal M, Weigel M, Huober J, Weder P, Steffens C, Lemster S, Stefek A, Ruhland F, Hofmann M, Schuster J, Simon W, Kronawitter U, Clemens M, Fehm T, Janni W, Latos K, Bauer W, Rosmann A, Bauer L, Lampe D, Heyl V, Hoffmann G, Lorenz-Salehi F, Hackmann J, Schlag R

Abstract

The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses.Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (? = 0.05, ? = 0.8) 379 events had to be observed in the bevacizumab arms.With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups.Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients.NCT 00567554, www.clinicaltrials.gov.