title: Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer.
abstract: OBJECTIVE
  NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2-positive breast cancer.
  
  
  METHODS
  Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS).
  
  
  RESULTS
  Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis.
  
  
  CONCLUSIONS
  DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen.
authors: Mayo Clinic, Jacksonville, FL 32224, USA. perez.edith@mayo.edu
authors: Edith A
authors: EA
authors: Perez
authors: Vera J
authors: VJ
authors: Suman
authors: Nancy E
authors: NE
authors: Davidson
authors: Julie R
authors: JR
authors: Gralow
authors: Peter A
authors: PA
authors: Kaufman
authors: Daniel W
authors: DW
authors: Visscher
authors: Beiyun
authors: B
authors: Chen
authors: James N
authors: JN
authors: Ingle
authors: Shaker R
authors: SR
authors: Dakhil
authors: Joanne
authors: J
authors: Zujewski
authors: Alvaro
authors: A
authors: Moreno-Aspitia
authors: Thomas M
authors: TM
authors: Pisansky
authors: Robert B
authors: RB
authors: Jenkins
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; D000068878:Trastuzumab