Disease-free and overall survival at 3.5 years for neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin and cyclophosphamide, for women with HER2 negative early breast cancer: ARTemis Trial

Research output: Contribution to journalArticlepeer-review


  • H. M. Earl
  • L Hiller
  • J Dunn
  • C Blenkinsop
  • L Grybowicz
  • A-L Vallier
  • I Gounaris
  • J Abraham
  • L Hughes-Davies
  • K McAdam
  • S Chan
  • R Ahmad
  • T Hickish
  • Daniel Rea
  • C. Caldas
  • J M S Bartlett
  • D A Cameron
  • E Provenzano
  • J Thomas
  • R L Hayward
  • ARTemis Investigators Group

Colleges, School and Institutes

External organisations

  • Warwick Clinical Trials Unit, University of Warwick, Coventry
  • Cambridge Clinical Trials Unit-Cancer Theme, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  • Department of Oncology, Queen Elizabeth Hospital King's Lynn NHS Foundation Trust, King's Lynn. UK.
  • Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge. UK.
  • Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, City Hospital, Nottingham NG5 1PB, UK
  • Department of Oncology, West Middlesex University Hospital, Isleworth. UK.
  • Bournemouth University
  • Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON, Canada.
  • Cancer Research Centre, University of Edinburgh, IGMM, Western General Hospital, Edinburgh. UK.
  • NIHR Cambridge Biomedical Research Centre
  • Department of Pathology, University of Edinburgh, Edinburgh. UK.
  • University of Cambridge
  • Cambridge Breast Cancer Research Unit, Cambridge University Hospitals NHS Foundation Trust


Background: The ARTemis trial previously reported that addition of neoadjuvant bevacizumab (Bev) to docetaxel followed by fluorouracil, epirubicin and cyclophosphamide (D-FEC) in HER2 negative breast cancer improved the pathological complete response (pCR) rate. We present disease-free (DFS) and overall survival (OS) with central pathology review.

Patients and Methods: Patients were randomised to 3 cycles of D followed by 3 cycles of FEC (D-FEC), ± 4 cycles of Bev (Bev+D-FEC). DFS and OS were analysed by treatment and by central pathology reviewed pCR and Residual Cancer Burden (RCB) categories.

Results: 800 patients were randomised (median follow-up 3·5 yrs (IQR 3·2-4·4)). DFS and OS were similar across treatment arms (DFS: hazard ratio (HR)=1·18 (95%CI 0·89-1·57), P =0·25. OS: HR = 1·26 (95%CI 0·90-1·76), P =0·19). Both local pathology report review and central histopathology review confirmed a significant improvement in DFS and OS for patients who achieved a pCR (DFS HR = 0·38 (95%CI 0·23-0·63), P <0·001: OS HR = 0·43 (95%CI 0·24-0·75), P =  0·003). However, significant heterogeneity was observed ( P =0·02); larger improvements in DFS were obtained with a pCR achieved with D-FEC than a pCR achieved with Bev+D-FEC. As RCB category increased, significantly worse DFS and OS was observed ( P for trend <0·0001), which effect was most marked in the ER negative group.

Conclusions: The addition of short course neoadjuvant Bev to standard chemotherapy did not demonstrate a DFS or OS benefit. Achieving a pCR with D-FEC is associated with improved DFS and OS but not when pCR is achieved with Bev+D-FEC. At the present time therefore, Bev is not recommended in early breast cancer (ClinicalTrials.gov number NCT01093235).

ClinicalTrials.gov: (NCT 01093235).


Original languageEnglish
JournalAnnals of Oncology
Publication statusPublished - 27 Apr 2017


  • Journal Article, ARTemis , breast cancer , bevacizumab , neoadjuvant chemotherapy