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

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

Abstract

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

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

Results: A total of 800 patients were randomized [median follow-up 3.5 years (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 class 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.

Keywords: ARTemis; bevacizumab; breast cancer; neoadjuvant chemotherapy.

© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Figures

Figure 1.
Figure 1.
Consort diagram.
Figure 2.
Figure 2.
Survival curves by randomized treatment arm. (A) Disease-free survival and (B) Overall survival.
Figure 3.
Figure 3.
Treatment effect by pathological response. (A) Disease-free survival from surgery and (B) Overall survival from surgery.

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