title: Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study.
abstract: OBJECTIVE
  To evaluate docetaxel or vinorelbine, both with trastuzumab, as first-line therapy of human epidermal growth factor receptor 2-positive advanced breast cancer.
  
  
  METHODS
  Patients naive to chemotherapy for advanced disease were randomly assigned to docetaxel 100 mg/m(2) day 1 or vinorelbine 30 to 35 mg/m(2) on days 1 and 8, both combined with trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance dose) on day 1 every 3 weeks. The primary end point was time to progression (TTP).
  
  
  RESULTS
  A total of 143 patients were randomly allocated to docetaxel, and 141 patients were assigned to vinorelbine. The median TTP for docetaxel and vinorelbine respectively was 12.4 months versus 15.3 months (hazard ratio [HR] = 0.94; 95% CI, 0.71 to 1.25; P = .67), median overall survival was 35.7 months versus 38.8 months (HR = 1.01; 95% CI, 0.71 to 1.42; P = .98), and the 1-year survival rate was 88% in both arms. Median time to treatment failure for study chemotherapy was 5.6 months versus 7.7 months (HR = 0.50; 95% CI, 0.38 to 0.64; P < .0001). The investigator-assessed overall response rate among 241 patients with measurable disease were 59.3% in both arms. More patients in the docetaxel arm discontinued therapy due to toxicity (P < .001). Significantly more treatment-related grade 3 to 4 febrile neutropenia (36.0% v 10.1%), leucopenia (40.3% v 21.0%), infection 25.1% v 13.0%), fever (4.3% v 0%), neuropathy (30.9% v 3.6%), nail changes (7.9% v 0.7%), and edema (6.5% v 0%) were reported with docetaxel.
  
  
  CONCLUSIONS
  The study failed to demonstrate superiority of any drug in terms of efficacy, but the vinorelbine combination had significantly fewer adverse effects and should be considered as an alternative first-line option.
authors.affiliation: Department of Oncology 5073, Rigshospitalet, 9 Blegdamsvej, 2100 Copenhagen, Denmark. michael.andersson@rh.regionh.dk
authors.forename: Michael
authors.initials: M
authors.lastname: Andersson
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lidbrink
authors.forename: Karsten
authors.initials: K
authors.lastname: Bjerre
authors.forename: Erik
authors.initials: E
authors.lastname: Wist
authors.forename: Kristin
authors.initials: K
authors.lastname: Enevoldsen
authors.forename: Anders B
authors.initials: AB
authors.lastname: Jensen
authors.forename: Per
authors.initials: P
authors.lastname: Karlsson
authors.forename: Ulla B
authors.initials: UB
authors.lastname: Tange
authors.forename: Peter G
authors.initials: PG
authors.lastname: Sørensen
authors.forename: Susanne
authors.initials: S
authors.lastname: Møller
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Sven T
authors.initials: ST
authors.lastname: Langkjer
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D000068878:Trastuzumab; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; D014747:Vinblastine; D000077235:Vinorelbine