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

HM Earl, L Hiller, JA Dunn, C Blenkinsop, L Grybowicz, AL Vallier, I Gounaris, JE Abraham, L Hughes-Davies, K McAdam, S Chan, R Ahmad, T Hickish, D Rea, C Caldas, JMS Bartlett, DA Cameron, E Provenzano, J Thomas, RL Haywardfor the ARTemis Investigators Group, Luca Gianni

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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. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Original languageEnglish
Pages (from-to)1817-1824
Number of pages8
JournalAnnals of Oncology
Volume28
Issue number8
DOIs
Publication statusPublished - 2017

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Earl, HM., Hiller, L., Dunn, JA., Blenkinsop, C., Grybowicz, L., Vallier, AL., Gounaris, I., Abraham, JE., Hughes-Davies, L., McAdam, K., Chan, S., Ahmad, R., Hickish, T., Rea, D., Caldas, C., Bartlett, JMS., Cameron, DA., Provenzano, E., Thomas, J., ... Gianni, L. (2017). 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. Annals of Oncology, 28(8), 1817-1824. https://doi.org/10.1093/annonc/mdx173