title: 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial.
abstract: BACKGROUND
  Trastuzumab has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. The standard of care is 1 year of adjuvant trastuzumab, but the optimum duration of treatment is unknown. We compared 2 years of treatment with trastuzumab with 1 year of treatment, and updated the comparison of 1 year of trastuzumab versus observation at a median follow-up of 8 years, for patients enrolled in the HERceptin Adjuvant (HERA) trial.
  
  
  METHODS
  The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant chemotherapy, adjuvant chemotherapy, or both in 5102 patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. The comparison of 2 years versus 1 year of trastuzumab treatment involved a landmark analysis of 3105 patients who were disease-free 12 months after randomisation to one of the trastuzumab groups, and was planned after observing at least 725 disease-free survival events. The updated intention-to-treat comparison of 1 year trastuzumab treatment versus observation alone in 3399 patients at a median follow-up of 8 years (range 0-10) is also reported. This study is registered with ClinicalTrials.gov, number NCT00045032.
  
  
  RESULTS
  We recorded 367 events of disease-free survival in 1552 patients in the 1 year group and 367 events in 1553 patients in the 2 year group (hazard ratio [HR] 0·99, 95% CI 0·85-1·14, p=0·86). Grade 3-4 adverse events and decreases in left ventricular ejection fraction during treatment were reported more frequently in the 2 year treatment group than in the 1 year group (342 [20·4%] vs 275 [16·3%] grade 3-4 adverse events, and 120 [7·2%] vs 69 [4·1%] decreases in left ventricular ejection fraction, respectively). HRs for a comparison of 1 year of trastuzumab treatment versus observation were 0·76 (95% CI 0·67-0·86, p<0·0001) for disease-free survival and 0·76 (0·65-0·88, p=0·0005) for overall survival, despite crossover of 884 (52%) patients from the observation group to trastuzumab therapy.
  
  
  CONCLUSIONS
  2 years of adjuvant trastuzumab is not more effective than is 1 year of treatment for patients with HER2-positive early breast cancer. 1 year of treatment provides a significant disease-free and overall survival benefit compared with observation and remains the standard of care.
  
  
  BACKGROUND
  F Hoffmann-La Roche (Roche).
authors.affiliation: Department of Medicine, European Institute of Oncology, Milan, Italy. aaron.goldhirsch@ieo.it
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Piccart-Gebhart
authors.forename: Evandro
authors.initials: E
authors.lastname: de Azambuja
authors.forename: Marion
authors.initials: M
authors.lastname: Procter
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Suter
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: David
authors.initials: D
authors.lastname: Cameron
authors.forename: Harald A
authors.initials: HA
authors.lastname: Weber
authors.forename: Dominik
authors.initials: D
authors.lastname: Heinzmann
authors.forename: Lissandra
authors.initials: L
authors.lastname: Dal Lago
authors.forename: Eleanor
authors.initials: E
authors.lastname: McFadden
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Luca
authors.initials: L
authors.lastname: Gianni
authors.forename: Richard
authors.initials: R
authors.lastname: Bell
authors.forename: Claus-Henning
authors.initials: CH
authors.lastname: Köhne
authors.forename: Anita
authors.initials: A
authors.lastname: Vindevoghel
authors.forename: Michael
authors.initials: M
authors.lastname: Andersson
authors.forename: A Murray
authors.initials: AM
authors.lastname: Brunt
authors.forename: Douglas
authors.initials: D
authors.lastname: Otero-Reyes
authors.forename: Santai
authors.initials: S
authors.lastname: Song
authors.forename: Ian
authors.initials: I
authors.lastname: Smith
authors.forename: Brian
authors.initials: B
authors.lastname: Leyland-Jones
authors.forename: Jose
authors.initials: J
authors.lastname: Baselga
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D055118:Medication Adherence; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab