National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 and the North Central Cancer Treatment Group (NCCTG) N9831 Trials

• In 2000, two landmark trials combined results:
  • That compared adjuvant chemotherapy with or without concurrent trastuzumab therapy:
    • In women with surgically removed HER2-positive breast cancer
• The NSABP B-31 trial:
  • Compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks (group 1) with the same regimen plus 52 weeks of trastuzumab given concurrently with paclitaxel (group 2)
• The NCCTG N9831 trial:
  • Conducted a similar study that compared three regimens:
    • Group A :
      • Doxorubicin and cyclophosphamide followed by weekly paclitaxel
    • Group B:
      • The same regimen in group A:
        • Followed by 52 weeks of trastuzumab given after paclitaxel
    • Group C:
      • The same regimen in group A:
        • Followed by 52 weeks of trastuzumab:
          • Initiated concurrently with paclitaxel
• The studies were combined to include:
  • A joint analysis comparing:
    • Groups 1 and group A (the control group) with groups 2 and group C (the trastuzumab group)
    • Group B was excluded
• Results by 2005 reported:
  • 394 events:
    • Recurrence
    • Second primary cancer
    • Death before recurrence
  • Of these events:
    • 133 were from the trastuzumab group
    • 261 were in the control group:
      • Hazard ratio, 0.48; P<0.0001
  • At 3 years:
    • The absolute difference in DFS between the trastuzumab group and the control group:
      • Was 12%
    • Trastuzumab therapy:
      • Was associated with a 33% reduction in the risk of death (P=0.015)
  • The interim analyses of these trials favored trastuzumab:
    • So strongly that the trials were stopped early and patients in the other arms were offered trastuzumab
  • Long-term analysis of these studies was reported in 2014:
    • At a median follow-up time of 8.4 years:
      • The addition of trastuzumab to chemotherapy:
        • Led to a 37% improvement in OS and
        • An increase in 10-year survival rate:
          • From 75.2% to 84%
      • Outcomes in DFS showed:
        • An improvement of 40% and
        • An increase in the 10-year DFS rate from 62.2% to 73.7%
• This study showed that all subgroups of HER2-positive patients (small and large tumors, hormone receptor-positive and -negative, low and high number of positive nodes, young and old patients):
  • Benefited from the addition of the targeted anti-HER2 agent:
    • Making trastuzumab an integral drug in the treatment of HER2-positive breast cancer

REFERENCES

1. Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014;32:3744-3752.
2. Romond E, Perez E, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673-1684.

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