Abstract P3-11-01: Neoadjuvant chemotherapy with or without bevacizumab or everolimus: Survival analysis of The HER2-negative cohort of the GEPARQUINTO study (GBG 44)
Authors: Gerber Bernd , Loibl Sibylle , Untch Michael , Eidtmann Holger , Rezai Mahdi , Fasching Peter A , Tesch Hans , Eggemann Holm , Schrader Iris , Kittel Kornelia , Hanusch Claus , Huober Jens , Solbach Christine , Jackisch Christian , Kunz Georg , Blohmer Jens-Uwe , Hauschild Maik , Fehm Tanja , Nekljudova Valentina , von Minckwitz Gunter 
Published: May 2015

Abstract
BACKGROUND: The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates from 14.9% to 18.4% (P=0.04) overall; specifically in patients with TNBC (27.9% to 39.3% (P=0.003) (von Minckwitz et al, NEJM 2012). No difference in pCR rate was observed for adding everolimus to paclitaxel patients who had no early response to neoadjuvant chemotherapy (Huober et al, Eur J Cancer 2013). Here, we present disease-free (DFS) and overall survival (OS) analyses.
PATIENTS AND METHODS: Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with 4xEC à 4x docetaxel with or without bevacizumab, 15 mg/Kg q3w before surgery. 408 patients not clinically responding to EC ± Bev were randomized to 12x weekly paclitaxel with or without everolimus 5mg/day. Patients with HR-positive tumors received endocrine treatment after surgery. 379 events are required to show a HR of 0.75 (α=0.05, ß=0.8) between the bevacizumab arms. 397 relapses and 234 deaths were observed after a median follow up of 3.8 years overall, of those 115 relapses and 75 deaths occurred in the non-responding cohort.
RESULTS: Overall, 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 = 0.780 for DFS and HR 0.974; P = 0.842 for OS) compared to patients receiving chemotherapy alone. Patients with TNBC showed no improvement in DFS (HR 0.991; P = 0.948) 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, cT4a-c, cT4d; pCR or not, CR, PR, NC after first 4 cycles chemotherapy) showed a benefit from bevacizumab. No difference in DFS (HR 0.997; P=0.987) and OS (HR 1.11; P=0.658) was observed for patients who had no early response to neoadjuvant chemotherapy receiving paclitaxel with or without everolimus overall as well as in subgroups.
CONCLUSIONS: Long-term results finally do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for patients who had no early response to neoadjuvant chemotherapy.
Citation Format: Bernd Gerber, Sibylle Loibl, Michael Untch, Holger Eidtmann, Mahdi Rezai, Peter A Fasching, Hans Tesch, Holm Eggemann, Iris Schrader, Kornelia Kittel, Claus Hanusch, Jens Huober, Christine Solbach, Christian Jackisch, Georg Kunz, Jens-Uwe Blohmer, Maik Hauschild, Tanja Fehm, Valentina Nekljudova, Gunter von Minckwitz. Neoadjuvant chemotherapy with or without bevacizumab or everolimus: Survival analysis of The HER2-negative cohort of the GEPARQUINTO study (GBG 44) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-01.