Oral etoposide in heavily pre-treated metastatic breast cancer: results from the ESME cohort and comparison with other chemotherapy regimens
- 231 Downloads
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.
KeywordsEtoposide 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.
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).
- 15.R Core Team (2017) R: A language and environment for statistical computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
- 20.Cortes J, O’Shaughnessy J, Loesch D et al (2011) Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet 377:914–923. https://doi.org/10.1016/S0140-6736(11)60070-6 CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Adunlin G, Cyrus JWW, Dranitsaris G (2015) Correlation between progression-free survival and overall survival in metastatic breast cancer patients receiving anthracyclines, taxanes, or targeted therapies: a trial-level meta-analysis. Breast Cancer Res Treat 154:591–608. https://doi.org/10.1007/s10549-015-3643-5 CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Liu L, Chen F, Zhao J, Yu H (2016) Correlation between overall survival and other endpoints in metastatic breast cancer with second- or third-line chemotherapy: Literature-based analysis of 24 randomized trials. Bull Cancer 103:336–344. https://doi.org/10.1016/j.bulcan.2016.01.002 CrossRefPubMedGoogle Scholar
- 30.Burzykowski T, Buyse M, Piccart-Gebhart MJ et al (2008) Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer. J Clin Oncol 26:1987–1992. https://doi.org/10.1200/JCO.2007.10.8407 CrossRefPubMedGoogle Scholar