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

The 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 North Central Cancer Treatment Group NCCTG N9831 trial conducted a similar study that compared three regimens: 
  • Group A:
    • Doxorubicin and cyclophosphamide followed by weekly paclitaxel
  • Group B:
    • Doxorubicin and cyclophosphamide followed by weekly paclitaxel, followed by 52 weeks of trastuzumab given after paclitaxel
  • Group C:
    • The same regimen in group A, followed by 52 weeks of trastuzumab initiated concurrentlywith 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, or death before recurrence):
  • Of these events, 133 were from the trastuzumab group and 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% and 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
  • Perez EA, Romond EH, Suman VJ, Jeong J-H, Sledge G, Geyer Jr GE, 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(33):3744-3752.
  • Romond E, Perez E, Bryant J, Suman VJ, Geyer Jr GE, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673-1684.

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