by Sharon T. Wilks, MD, FACP
Target therapy with use of monoclonal antibody therapy has become a rapidly evolving form of treatment in many forms of cancer – breast cancer particularly.
In 2005, several reports discussed the usefulness of two forms of monoclonal therapy, trastuzumab (also referred to as Herceptin®) and bevacizumab (Avas-tin®). Trastuzumab was approved by the U.S. Food and Drug Administration in 1998 for use in metastatic breast cancer that is HER2/neu positive as a result of its strong Phase III studies. Those studies showed activity in poor risk breast cancer when used singly or in combination with anthracycline and/or taxane-based therapy.
Between 20% and 30% of all new breast cancer cases are HER2/neu positive. The HER2 gene is a tyrosine kinase growth factor receptor. Overexpression of this gene in breast cancer is associated with high risk of relapse and early death secondary to breast cancer recurrence (see Figures 1 and 2).
This area of the tumor cell can be targeted through immune mechanisms including antibody-dependent cellular cytotoxicity, or ADCC, via the drug trastuzumab. Many studies have shown trastuzumab’s value as monotherapy and when used in combination with chemotherapy in the metastatic setting. During the past year, five trials presented at two large meetings – the American Society of Clinical Oncology and the San Antonio Breast Cancer Society – showed strong evidence of the value of trastuzumab in the adjuvant setting for early stages of breast cancer when tumors are HER2/ neu positive.
Over 50% reduction of recurrence has been demonstrated in trials when this drug is administered concurrently or se-quentially after anthracycline and taxane-based therapy. Although follow-up for these trials currently is less than four years, there is a hope that this form of antibody may be curative in this group of high risk, poor prognostic breast can-cer patients.
Rigorous cardiac monitoring is neces-sary (most of the studies required assessment every three months for left ventricular ejection fractions) as this drug, par-ticularly when used concurrently with anthracycline and taxane-based therapy, induces congestive heart failure in about 2% to 4% of patients. However, with no reports of alopecia, myelotoxicity, or severe gastrointestinal effects, minimal other drug toxicities are seen.
Also reported in the same group of meetings in 2005 was bevacizumab, another monoclonal antibody. This drug, when administered with Paclitaxel in first-line metastatic breast cancer treatment, doubled median survival rates from six months to just over 11 months.
This antibody targets vascular endothelial growth factor, or VEGF (see Figure 3), the presence of which portends higher risks of relapse and tumor growth. Through immune mechanisms, this VEGF ligand (see Figure 4) can be targeted and tumor control can result. A large cooperative group study known as E2100 was the first to demonstrate bevacizumab’s usefulness in advanced breast cancer. The significant benefits noted by researchers have prompted plans for a new adjuvant study evaluating its role in the early stages of breast cancer.
The idea that these targeted therapies can work in advanced forms of breast cancer – often resistant to more toxic therapies – is exciting, and these success stories give us hope that we can effectively use less harmful agents in cancer control. Costs remain a significant issue, with charges of $2,000 to $6,000 per treatment.
Additional information on these stu-dies is available at www.sabcs.org and www.asco.org.
Dr. Wilks, a hematologist/ medical oncologist, is chair for both the Cancer Commit-tee for Baptist Health System and the Alamo City Breast Cancer Council. She works with the Cancer Care Centers of South Texas.
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