Breast Cancer Research and Treatment

, Volume 173, Issue 2, pp 397–406 | Cite as

Oral etoposide in heavily pre-treated metastatic breast cancer: results from the ESME cohort and comparison with other chemotherapy regimens

  • Luc CabelEmail author
  • Matthieu Carton
  • Bianca Cheaib
  • Jean-Yves Pierga
  • Florence Dalenc
  • Audrey Mailliez
  • Christelle Levy
  • William Jacot
  • Marc Debled
  • Marianne Leheurteur
  • Isabelle Desmoulins
  • Claudia Lefeuvre
  • Anthony Gonçalves
  • Lionel Uwer
  • Jean-Marc Ferrero
  • Jean-Christophe Eymard
  • Thierry Petit
  • Marie-Ange Mouret-Reynier
  • Geneviève Perrocheau
  • Irwin Piot
  • David Pérol
  • Gaëtane Simon
  • Florence Lerebours
Clinical trial



HER2-negative metastatic breast cancer (MBC) is a common setting in which chemotherapy could be effective even in later lines of treatment. Oral etoposide has demonstrated clinical activity in this setting in small-scale studies, but its efficacy has not been compared to that of other chemotherapy regimens.


We used the ESME database (Epidemiological Strategy and Medical Economics), a real-life national French multicentre cohort of MBC patients initiating therapy between 1 January 2008 to 31 December 2014. HER2-negative MBC patients who received oral etoposide as > 3rd chemotherapy line and for more than 14 days were included. Primary objective was progression-free survival (PFS); secondary objectives were overall survival (OS), and propensity-score matched Cox models including comparison with other therapies in the same setting.


Three hundred forty-five out of 16,702 patients received oral etoposide and 222 were eligible. Median PFS was 3.2 months [95% CI 2.8–4] and median OS 7.3 months [95% CI 5.7–10.3]. Median PFS did not significantly differ according to the therapeutic line. The only prognostic factor for both PFS and OS was the MBC phenotype (hormone receptor-positive versus triple-negative, HR = 0.71 [95% CI 0.52–0.97], p = 0.028 for PFS and HR = 0.65 [0.46–0.92], p = 0.014 for OS). After matching for the propensity score, no differential effect on PFS or OS was observed between oral etoposide and other chemotherapy regimens administered in the same setting (HR = 0.94 [95% CI 0.77–1.15], p = 0.55 for PFS and HR = 1.10 [95% CI 0.88–1.37], p = 0.40 for OS).


Oral etoposide retains some efficacy in selected heavily pre-treated patients with HER2-negative MBC, with the advantages of oral administration.


Etoposide Metastatic breast cancer Oral drug 



This work was supported by R&D UNICANCER. The ESME MBC database is supported by an industrial consortium (Roche, Pierre Fabre, Pfizer, AstraZeneca, MSD, Eisai and Daiichi Sankyo). Data collection, analyses and publications are totally managed by R&D UNICANCER independently of the industrial consortium.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The present analysis was approved by an independent ethics committee (Comité De Protection Des Personnes Sud-Est II- 2015-79). No formal dedicated informed consent was required but all patients had approved the re-use of their electronically recorded data. In compliance with French regulations, the ESME MBC database was authorized by the French data protection authority (Authorization No. 1704113).

Supplementary material

10549_2018_5017_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 14 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Luc Cabel
    • 1
    Email author
  • Matthieu Carton
    • 1
  • Bianca Cheaib
    • 2
  • Jean-Yves Pierga
    • 1
  • Florence Dalenc
    • 3
  • Audrey Mailliez
    • 4
  • Christelle Levy
    • 5
  • William Jacot
    • 6
  • Marc Debled
    • 7
  • Marianne Leheurteur
    • 8
  • Isabelle Desmoulins
    • 9
  • Claudia Lefeuvre
    • 10
  • Anthony Gonçalves
    • 11
  • Lionel Uwer
    • 12
  • Jean-Marc Ferrero
    • 13
  • Jean-Christophe Eymard
    • 14
  • Thierry Petit
    • 15
  • Marie-Ange Mouret-Reynier
    • 16
  • Geneviève Perrocheau
    • 17
  • Irwin Piot
    • 18
  • David Pérol
    • 19
  • Gaëtane Simon
    • 18
  • Florence Lerebours
    • 1
  1. 1.Institut CurieSaint-CloudFrance
  2. 2.Gustave RoussyVillejuifFrance
  3. 3.Institut Claudius regaud-IUCT-OncopoleToulouseFrance
  4. 4.Centre Oscar LambretLilleFrance
  5. 5.Centre Francois BaclesseCaenFrance
  6. 6.ICMMontpellierFrance
  7. 7.Institut BergonieBordeauxFrance
  8. 8.Centre Henri BecquereRouenFrance
  9. 9.Centre Georges-Francois LeclercDijonFrance
  10. 10.Centre Eugene MarquisRennesFrance
  11. 11.Institut Paoli-CalmettesMarseilleFrance
  12. 12.ICLVandoeuvre-les-NancyFrance
  13. 13.Centre Antoine LacassagneNiceFrance
  14. 14.Institut Jean GodinotReimsFrance
  15. 15.Centre Paul StraussStrasbourgFrance
  16. 16.Centre Jean PerrinClermont-FerrandFrance
  17. 17.ICONantesFrance
  18. 18.R&D UnicancerParisFrance
  19. 19.Centre Léon BérardLyonFrance

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