Trastuzumab

Herceptin (Roche)
vials containing 150 mg lyophilised powder
Approved indication: breast cancer
Australian Medicines Handbook Section 14.1

In up to 30% of patients with breast cancer there is an over expression of the HER2 gene. This oncogene codes for a receptor to epidermal growth factor. Trastuzumab is a monoclonal antibody which can block this receptor. This inhibits the growth of breast cancer cells.

Trastuzumab is a humanised murine antibody produced by recombinant technology. It is given as a slow intravenous infusion. The first loading dose is given over 90 minutes. If this is well tolerated, subsequent weekly infusions can be given over 30 minutes. These infusions are repeated until the cancer progresses.

The half-life of trastuzumab is approximately six days, but a steady state is not reached for 16-32 weeks. As trastuzumab has non-linear pharmocokinetics its clearance decreases as the dose increases. Serum concentrations are also increased if the drug is given with paclitaxel.

Trastuzumab has been studied as monotherapy for women with metastatic tumours that over express HER2. The 222 women in this study had failed to respond to chemotherapy, but 15% showed some response to trastuzumab.

The drug has also been used in combination with chemotherapy for metastatic breast cancer. In terms of the median time before the disease progressed, trastuzumab had significant advantages. Trastuzumab with paclitaxel delayed progression more than paclitaxel alone, and with an anthracycline and cyclophosphamide it delayed progression more than that combination alone. Overall, adding trastuzumab to chemotherapy increased the median time to disease progression by 61%.

Trastuzumab is a protein, so patients can develop hypersensitivity reactions. Serious reactions have occurred during the infusions and many other patients will experience fevers or chills. There is a risk of cardiotoxicity, and approximately9% of patients treated with trastuzumab will develop heart failure. This risk may be increased in patients treated with anthracyclines so, for combination regimens, only the taxanes can be used with trastuzumab. Common adverse reactions include nausea, vomiting and diarrhoea.

Trastuzumab appears to improve the survival of women with metastatic breast cancer who have over expression of the HER2 oncogene, but not all women will benefit. Only a small number (8/222) of women had a complete response to monotherapy. In that study, the median time to tumour progression was only three months. When trastuzumab is given with paclitaxel the median time to progression is seven months. Although this increases one year survival from 62% to 73%, the difference is not statistically significant.