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 Dunn; C Blenkinsop; L Grybowicz; A-L Vallier; I Gounaris; J 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

doi:10.1093/annonc/mdx173

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 Dunn, C Blenkinsop, L Grybowicz, A-L Vallier, I Gounaris, J 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 HaywardARTemis Investigators Group

Cancer Research UK Clinical Trials Unit

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Abstract

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 language	English
Journal	Annals of Oncology
DOIs	https://doi.org/10.1093/annonc/mdx173
Publication status	Published - 27 Apr 2017

Keywords

Journal Article
ARTemis
breast cancer
bevacizumab
neoadjuvant chemotherapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Earl, H. M., Hiller, L., Dunn, J., Blenkinsop, C., Grybowicz, L., Vallier, A.-L., Gounaris, I., Abraham, J., Hughes-Davies, L., McAdam, K., Chan, S., Ahmad, R., Hickish, T., Rea, D., Caldas, C., Bartlett, J. M. S., Cameron, D. A., Provenzano, E., Thomas, J., ... ARTemis Investigators Group (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. https://doi.org/10.1093/annonc/mdx173

@article{df7626293d3743a2a0b7e2532c7312a1,

title = "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",

abstract = "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).",

keywords = "Journal Article, ARTemis , breast cancer , bevacizumab , neoadjuvant chemotherapy",

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

year = "2017",

month = apr,

day = "27",

doi = "10.1093/annonc/mdx173",

language = "English",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Oxford University Press",

}

Earl, HM, Hiller, L, Dunn, J, Blenkinsop, C, Grybowicz, L, Vallier, A-L, Gounaris, I, Abraham, J, Hughes-Davies, L, McAdam, K, Chan, S, Ahmad, R, Hickish, T, Rea, D, Caldas, C, Bartlett, JMS, Cameron, DA, Provenzano, E, Thomas, J, Hayward, RL & ARTemis Investigators Group 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. https://doi.org/10.1093/annonc/mdx173

TY - JOUR

T1 - 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:

T2 - ARTemis Trial

AU - Earl, H. M.

AU - Hiller, L

AU - Dunn, J

AU - Blenkinsop, C

AU - Grybowicz, L

AU - Vallier, A-L

AU - Gounaris, I

AU - Abraham, J

AU - Hughes-Davies, L

AU - McAdam, K

AU - Chan, S

AU - Ahmad, R

AU - Hickish, T

AU - Rea, D

AU - Caldas, C.

AU - Bartlett, J M S

AU - Cameron, D A

AU - Provenzano, E

AU - Thomas, J

AU - Hayward, R L

AU - ARTemis Investigators Group

PY - 2017/4/27

Y1 - 2017/4/27

N2 - 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).

AB - 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).

KW - Journal Article

KW - ARTemis

KW - breast cancer

KW - bevacizumab

KW - neoadjuvant chemotherapy

U2 - 10.1093/annonc/mdx173

DO - 10.1093/annonc/mdx173

M3 - Article

C2 - 28459938

SN - 0923-7534

JO - Annals of Oncology

JF - Annals of Oncology

ER -