• Trastuzumab in the adjuvant setting:
    • Has been shown to significantly improve DFS and OS and has become the standard of care for patients with HER-2-positive breast cancer
  • Newer agents and combination dual anti-HER-2 therapy have been investigated:
    • The Adjuvant Lapatinib and / or Trastuzumab Treatment Optimisation (ALLTO) trial:
      • Investigated the role of lapatinib, a dual tyrosine kinase inhibitor of both EGFR and ErbB2:
        • As a single agent or in combination with trastuzumab compared with trastuzumab as a single agent in the treatment of HER-2-positive tumors
      • The study failed to show a statistically significant improvement in:
        • DFS with dual HER-2 blockade compared with trastuzumab alone
      • Patients who received lapatinib experienced:
        • More diarrhea, cutaneous rash, and hepatic toxicity
      • The results of this trial were unexpected:
        • As dual therapy with trastuzumab and lapatinib in the neoadjuvant setting showed promising results
    • A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 (HER2)-Positive Primary Breast Cancer, the APHINITY trial:
      • Assessed  the outcomes and effectiveness of incorporating the second generation anti-HER-2 monoclonal antibody, pertuzumab, together with trastuzumab in the adjuvant setting)
      • The study revealed that pertuzumab added to trastuzumab and chemotherapy:
        • Significantly improved the rates of invasive-disease-free survival among patient with HER-2 positive breast cancer:
          • This was most apparent in patients with node positive disease or hormone receptor negativity
        • Specifically, dual anti-HER-2 therapy increased the:
          • 3-year disease-free survival from 93.2% to 94.1% (HR 0.81, 95% CI 0.66-1.00, p=0.045):
            • This difference is clinically modest
          • In women with clinically node positive disease:
            • The improvement was also modest, increasing from 90.2% to 92% (HR0.77, 95%CI 0.62-092, p=0.02)
        • These studies highlight the importance of considering extent of benefit and risk of associated side effects from treatment
        • Future studies are needed to stratify patients into those that benefit from standard treatment and those that benefit from more intensive treatment

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