title: Randomized phase II study comparing efficacy and safety of combination-therapy trastuzumab and docetaxel vs. sequential therapy of trastuzumab followed by docetaxel alone at progression as first-line chemotherapy in patients with HER2+ metastatic breast cancer: HERTAX trial.
abstract: BACKGROUND
  Because chemotherapy for metastatic breast cancer (MBC) is associated with relevant toxicity, sequential monotherapy trastuzumab followed by cytotoxic therapy at disease progression might be an attractive approach.
  
  
  METHODS
  In a multicenter phase II trial, 101 patients with overexpression of human epidermal growth factor receptor 2 (HER2(+)) MBC were randomized between combination-therapy trastuzumab (Herceptin) plus docetaxel (H+D) and sequential therapy of single-agent trastuzumab followed at disease progression by docetaxel alone (H→D) as first-line chemotherapy for metastatic disease. The primary endpoint was progression-free survival (PFS) after completed sequential or combination therapy.
  
  
  RESULTS
  For the H+D group the median PFS was 9.4 vs. 9.9 months for the H→D group and 1-year PFS rates were 44% vs. 35%, respectively. However the overall response rates (ORRs) were 79% vs. 53%, respectively (P = .016), and overall survival was 30.5 vs. 19.7 months, respectively (P = .11). In the H→D group, response rates to monotherapy trastuzumab and subsequent docetaxel were 34% and 39%, respectively, with a median PFS during single-agent trastuzumab of 3.9 months. The incidence and severity of neuropathy were significantly higher in the H+D group. Retrospective analysis of trastuzumab treatment beyond progression (applied in 46% of patients in the H+D group and 37% in the H→D group) showed a correlation with longer overall survival in both treatment arms (36.0 vs. 18.0 months and 30.3 vs. 18.6 months, respectively).
  
  
  CONCLUSIONS
  First-line treatment in patients with MBC with H→D resulted in a similar PFS compared with H+D, but the response rate was lower and the overall survival nonsignificantly shorter.
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands. a.hamberg@erasmusmc.nl
authors.forename: Paul
authors.initials: P
authors.lastname: Hamberg
authors.forename: Monique M E M
authors.initials: MM
authors.lastname: Bos
authors.forename: Hans J J
authors.initials: HJ
authors.lastname: Braun
authors.forename: Jacqueline M L
authors.initials: JM
authors.lastname: Stouthard
authors.forename: Gert A
authors.initials: GA
authors.lastname: van Deijk
authors.forename: Frans L G
authors.initials: FL
authors.lastname: Erdkamp
authors.forename: Iris N
authors.initials: IN
authors.lastname: van der Stelt-Frissen
authors.forename: Marijke
authors.initials: M
authors.lastname: Bontenbal
authors.forename: Geert-Jan M
authors.initials: GJ
authors.lastname: Creemers
authors.forename: Johanneke E A
authors.initials: JE
authors.lastname: Portielje
authors.forename: Johannes F M
authors.initials: JF
authors.lastname: Pruijt
authors.forename: Olaf J L
authors.initials: OJ
authors.lastname: Loosveld
authors.forename: Willem M
authors.initials: WM
authors.lastname: Smit
authors.forename: Erik W
authors.initials: EW
authors.lastname: Muller
authors.forename: Paul I M
authors.initials: PI
authors.lastname: Schmitz
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.forename: Jan G M
authors.initials: JG
authors.lastname: Klijn
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003131:Combined Modality Therapy; D018450:Disease Progression; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D007167:Immunotherapy; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000008:administration & dosage*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D000077143:Docetaxel; D000068878:Trastuzumab