Duration of Anti-HER2 Therapy

• A combination of the North Central Cancer Treatment Group (NCCTG) N9831 trial and the National Adjuvant Breast and Bowel Project (NSABP) B-31 clinical trials:
  • Showed a:
    • 40% improvement:
      • In disease-free survival
    • 37% improvement:
      • In overall survival:
        • With the addition of a year of trastuzumab:
          • To doxorubicin, cyclophosphamide, and paclitaxel chemotherapy
    • Improvements in disease-free survival and overall survival:
      • Were observed in all patients:
        • Independent of hormone receptor status and extent of nodal involvement
• The duration of trastuzumab therapy has been debated:
  • The Herceptin Adjuvant (HERA) trial:
    • Evaluated 1 year of therapy versus 2 years of therapy:
      • Did not show a significant difference:
        • In disease-free survival and overall survival between the two groups
  • The Protocol of Herceptin Adjuvant with Reduced Exposure, a Randomized Comparison of 6 Months vs 12 Months in All Women Receiving Adjuvant Herceptin (PHARE) trial:
    • Evaluated 6 months of trastuzumab compared to 12 months:
      • At 3.5-year follow-up:
        • The shorter trastuzumab course did not have a worse survival outcome compared to the 12-month course
  • A Cochrane meta-analysis of eight trials:
    • Including more than 11,900 patients:
      • With early and locally advanced HER2-positive breast cancer:
        • Also found improvements in:
          • Disease-free survival (HR 0.66) and overall survival (HR 0.60) with:
            • Chemotherapy plus trastuzumab versus chemotherapy alone or trastuzumab alone regimens
• Two small trials administering trastuzumab for less than six months:
  • Did not differ from trials with longer treatment duration and had less trastuzumab-associated toxicities:
    • However, given these studies’ small cohort size and short follow-up:
      • 12 months of trastuzumab treatment remains standard therapy

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(33):3744-3752.
2. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013;382(9897):1021-1028.
3. Pivot X, Romieu G, Debled M, et al. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Lancet Oncol. 2013;14(8):741-748.
4. Moja L, Tagliabue L, Balduzzi S, et al. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev. 2012;4:CD006243.

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