Second-line single-agent chemotherapy in human epidermal growth factor receptor 2-negative metastatic breast cancer: a systematic review

Fabio Puglisi, Daniel Rea, Michel A. Kroes, Paolo Pronzato

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No ‘gold standard’ exists for single-agent chemotherapy of human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer (MBC) in the second-line. The objective of this systematic review is to identify and appraise overall survival (OS), progression-free survival (PFS), time to progression (TTP) and Grade ≥3 adverse event evidence for single-agent chemotherapy in this setting.


MEDLINE, Embase and the Cochrane Library were searched to October 2013, and PubMed October 2013 to November 2014. Electronic database searches were supplemented with hand searching of reference lists and conferences. Eligible randomised controlled trials (RCTs) employed at least one single-agent chemotherapy treatment, enrolled HER2-negative or unselected MBC patients who had progressed following first-line chemotherapy within the metastatic setting, and reported outcomes of interest for the second-line setting.


Fifty-three RCTs were included in total, with most containing mixed populations by HER2 status and treatment line. Fourteen studies reported data specifically for second- and later-line treatment within the metastatic setting. Median overall survival (OS) in most trials was 8–13 months. Only one trial reported a significant difference between studied interventions in the second-line metastatic setting: nab-paclitaxel (n = 131) conferred a statistically significant OS advantage vs. three-weekly paclitaxel (n = 136) (median OS 13.0 vs. 10.7 months, respectively; hazard ratio 0.73, p = 0.024) and improved overall safety.


One RCT demonstrated significant benefit in this setting in confirmed HER2-negative MBC alongside favourable safety. Treatment line terminology was imprecise. To reliably inform patient treatment decisions, quality-of-life data are needed and precise OS estimation according to underlying patient characteristics.
Original languageEnglish
Pages (from-to)36-49
JournalCancer Treatment Reviews
Early online date8 Dec 2015
Publication statusPublished - Feb 2016


  • Second-Line
  • HER2-negative
  • Metastatic breast cancer
  • Monotherapy
  • Systematic review
  • Randomised controlled trials


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