Anti-HER2 Therapy

• Pertuzumab:
  • Is approved for use preoperatively in advanced disease and in the metastatic setting
• Trastuzumab:
  • Is approved for use in neoadjuvant, adjuvant, and metastatic settings
• Ado-trastuzumab-emtansine and lapatinib:
  • Are approved for use in the metastatic setting:
    • Among patients who have progressed on previous lines of systemic chemotherapy, including trastuzumab
• Lapatinib:
  • Is an oral small molecule receptor tyrosine kinase inhibitor of both:
    • HER2 and EGFR
• Trastuzumab and pertuzumab:
  • Are humanized monoclonal antibodies:
    • That target the extracellular HER2 domain
  • However, pertuzumab:
    • Binds to a different HER2 epitope than trastuzumab:
      • Resulting in more HER2 blockade when they are given together
• Ado-trastuzumab-emtansine:
  • Is a HER2-antibody drug conjugate:
    • That incorporates trastuzumab with emtansine:
      • A microtubule inhibitor DM1:
    • The conjugate:
      • Which is linked via a stable thioether linker:
        • Allows for selective delivery into HER2 overexpressing cells:
          • Resulting in cell cycle arrest and apoptosis

REFERENCES

1. Lin JJ, Cardarella S, Lydon CA, et al. Five-year survival in EGFR-mutant metastatic lung adenocarcinoma treated with EGFR-TKIs. J Thorac Oncol. 2016;11(4):556-565.
2. Weickhardt AJ, Price TJ, Chong G, et al. Dual targeting of the epidermal growth factor receptor using the combination of cetuximab and erlotinib: preclinical evaluation and results of the phase II DUX study in chemotherapy-refractory, advanced colorectal cancer. J Clin Oncol. 2012;30(13):1505-1512.
3. Jiang H, Rugo HS. Human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer: how the latest results are improving therapeutic options. Ther Adv Med Oncol. 2015;7(6):321-339.

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