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

Ann Oncol. 2014 Dec;25(12):2363-2372. doi: 10.1093/annonc/mdu455. Epub 2014 Sep 15.


Background: 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 and methods: 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 (α = 0.05, β = 0.8) 379 events had to be observed in the bevacizumab arms.

Results: 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.

Conclusions: 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.

Clinical trial number: NCT 00567554,

Trial registration: NCT00567554.

Keywords: bevacizumab; disease-free survival; everolimus; neoadjuvant chemotherapy; overall survival.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bevacizumab
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Chemotherapy, Adjuvant
  • Drug Therapy, Combination
  • Everolimus
  • Female
  • Humans
  • Middle Aged
  • Receptor, ErbB-2 / metabolism
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • Survival Analysis


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Everolimus
  • Receptor, ErbB-2
  • Sirolimus

Associated data