Trastuzumab (Herceptin)

• About 20% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2)
  • associated with an adverse prognosis
• Trastuzumab:
  • is a humanised monoclonal antibody that is directed against the external domain of HER2
  • leads to an improvement in survival when given in combination with paclitaxel and docetaxel in patients with metastatic disease. Also achieves high rates of tumour regression with other drugs including vinorelbine
  • leads to reduction in risk of early recurrence by about 50% when given with or after adjuvant chemotherapy for a year
  • associated with an increased risk of cardiotoxicity (mainly congestive heart failure)
    • risk is increased when given with chemotherapy, especially with anthracycline
      • there is also a slight risk of cardiotoxicity when given after anthracycline, but higher when given concurrently

Also evidence that achieves high response rates in combination with neoadjuvant chemotherapy in breast cancers that overexpressed HER2.

NICE have recommended that (4,5):

• trastuzumab, given at 3-week intervals for 1 year or until disease recurrence (whichever is the shorter period), is recommended as a treatment option for women with early-stage HER2-positive breast cancer following surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (if applicable)
• cardiac function should be assessed prior to the commencement of therapy and trastuzumab treatment should not be offered to women who have a left ventricular ejection fraction (LVEF) of 55% or less, or who have any of the following:
  • a history of documented congestive heart failure
  • high-risk uncontrolled arrhythmias
  • angina pectoris requiring medication
  • clinically significant valvular disease
  • evidence of transmural infarction on electrocardiograph (ECG)
  • poorly controlled hypertension
  • cardiac functional assessments should be repeated every 3 months during trastuzumab treatment. If the LVEF drops by 10% from baseline and to below 50% then trastuzumab treatment should be suspended. A decision to resume trastuzumab therapy should be based on a further cardiac assessment and a fully informed discussion of the risks and benefits between the individual patient and their clinician

Also NICE have stated that "..Trastuzumab in combination with an aromatase inhibitor is not recommended for first-line treatment in postmenopausal women with metastatic hormone- receptor- positive breast cancer that overexpresses HER2.." (6)

Notes:

• adjuvant therapy is following surgery; neoadjuvant therapy is prior to surgery

Reference:

1. BMJ. 2006 Jan 28;332(7535):223-4.
2. BMJ 2006;332:34-37
3. BMJ 2006;332:101-103.
4. NICE (August 2006).trastuzumab.
5. NICE (February 2009).Early and locally advanced breast cancer - dagnosis and treatment
6. NICE (June 2012). Lapatinib or trastuzumab in combination with an aromatase inhibitor for the first-line treatment of metastatic hormonereceptor- positive breast cancer that overexpresses HER2