title: "New" metastases are associated with a poorer prognosis than growth of pre-existing metastases in patients with metastatic breast cancer treated with chemotherapy.
abstract: Progression-free survival (PFS) and overall survival (OS) endpoints often only weakly correlate. This analysis investigates how different progression events impact on OS, using data from two phase 3 studies with eribulin in women with advanced/metastatic breast cancer (MBC).
  
  
  
  In Study 301, 1102 women with ≤2 prior chemotherapies for advanced/MBC were randomized to eribulin mesylate (1.4 mg/m(2) on days 1 and 8 every 21 days) or capecitabine (1.25 g/m(2) twice daily on days 1-14 every 21 days). Study 305/EMBRACE enrolled 762 patients following two to five prior chemotherapies for advanced/MBC, randomized to eribulin (as above) or treatment of physician's choice. We analyzed OS and PFS post hoc for patients whose disease progressed due to development of "new" metastases, growth of pre-existing lesions, and patients with no reported disease progression.
  
  
  
  In both clinical studies, development of new metastases was associated with an increased risk of death (p < 0.0001). The time to development of new metastasis or death was significantly longer with eribulin than the comparator in Study 305 (p = 0.0017), but not in Study 301 (p = 0.46). Significantly longer OS was observed in the eribulin compared with the comparator arm for the new metastases subgroup in Study 301 (p = 0.008), but not in Study 305 (p = 0.16), compared with other progression subgroups.
  
  
  
  Patients with MBC progressing with new metastases have a worse prognosis than those whose disease progresses due to growth of existing lesions or patients with no reported disease progression. These findings have potentially important implications for the interpretation of clinical study data and clinical practice.
  
  
  
  ClinicalTrials.gov registration IDs: Study 301: NCT00337103 ; Study 305: NCT00388726 .
authors.affiliation: Section of Oncology and Clinical Research, Leeds Institute of Cancer and Pathology, University of Leeds and Leeds Teaching Hospitals Trust, Leeds, UK. C.J.Twelves@leeds.ac.uk.|St James' Institute of Oncology, St James' University Hospital, University of Leeds, Bexley Wing, Level 4, Beckett Street, Leeds, UK. C.J.Twelves@leeds.ac.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: Twelves
authors.affiliation: Department of Oncology, Vall d'Hebron Institute of Oncology, Barcelona, Spain.|Department of Oncology, Ramon y Cajal University Hospital, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Section of Hematology/Oncology, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kaufman
authors.affiliation: Department of Medicine, University of Montreal, Montreal, QC, Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Yelle
authors.affiliation: Medical Oncology Clinic, Medicine Department, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Awada
authors.affiliation: Oncology Imaging, Eisai Inc., Woodcliff Lake, NJ, USA.
authors.forename: Terri A
authors.initials: TA
authors.lastname: Binder
authors.affiliation: Oncology PCU, Clinical Development, Eisai Inc., Woodcliff Lake, NJ, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Olivo
authors.affiliation: Department of Medical Affairs, Eisai Inc., Woodcliff Lake, NJ, USA.
authors.forename: James
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Medical Oncology, US Oncology, Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA.
authors.forename: Joyce A
authors.initials: JA
authors.lastname: O'Shaughnessy
authors.affiliation: Section of Oncology and Clinical Research, Leeds Institute of Cancer and Pathology, University of Leeds and Leeds Teaching Hospitals Trust, Leeds, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Jove
authors.affiliation: Division of Hematology/Oncology, Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000069287:Capecitabine / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005663:Furans / Q000627:therapeutic use; D006801:Humans; D007659:Ketones / Q000627:therapeutic use; D011379:Prognosis; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D000069287:Capecitabine; D005663:Furans; D007659:Ketones; C490954:eribulin; D000095662:Polyether Polyketides