SUMMARY OF ADJUVANT ANTI-HER-2 THERAPY

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