title: Second-line single-agent chemotherapy in human epidermal growth factor receptor 2-negative metastatic breast cancer: A systematic review.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oncology, University Hospital of Udine, Piazzale S. Maria della Misericordia, n. 15, 33100 Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Piazzale Kolbe, n. 3, 33100 Udine, Italy. Electronic address: fabio.puglisi@uniud.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Puglisi
authors.affiliation: Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: d.w.rea@bham.ac.uk.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rea
authors.affiliation: DRG Abacus, Unit 6, Talisman Business Centre, Talisman Road, Bicester, Oxfordshire OX26 6HR, UK. Electronic address: mkroes@dresourcesgroup.com.
authors.forename: Michel A
authors.initials: MA
authors.lastname: Kroes
authors.affiliation: IRCCS Azienda Ospedaliera Universitaria San Martino - IST, Largo Rosanna Benzi, 10, 16132 Genova, Italy. Electronic address: paolo.pronzato@hsanmartino.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pronzato
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000066491:Clinical Decision-Making; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: HER2-negative; Metastatic breast cancer; Monotherapy; Randomised controlled trials; Second-line; Systematic review