Clinical trial of antibody-guided breast cancer drug promising

Posted Dec 12, 2009 by Elizabeth Cunningham Perkins
A new antibody guided anti-cancer drug has shown encouraging Phase 2 clinical trial results, shrinking or stabilizing HER2-positive metastatic cancerous breast tumors in about half of the cases.
Metastatic breast cancer in pleural fluid
Metastatic breast cancer in pleural fluid
Ian Krop, MD, PhD, the principal researcher in a study at the Dana-Farber Cancer Institute of Harvard Medical School, found that a hybrid drug called T-DM1 achieved a total clinical benefit rate of 53 percent when administered to a test group of patients whose HER2-positive cancer had developed resistance to FDA-approved chemotherapy agents such as trastuzumab and lapatinib.
According to the Mayo Clinic website, HER2-positive cancer is any cancer that tests positive for a cancer cell growth promoting protein called human epidermal growth factor receptor-2, abbreviated HER2. Cancer cells produce excess HER2 in 20 to 30 percent of cases because of a gene mutation.
Krops findings, being presented on Saturday, Dec. 12, at the 32nd annual CTRC-AACR San Antonio Breast Cancer Symposium, show that T-DM1 shrank tumors by 30 percent or more in 40 percent of a group of 110 women with confirmed HER2-positive cancers. Tumor growth was halted for at least six months in another 13 percent of the test group.
A hybrid anticancer agent is comprised of a cancer cell targeting agent and an antibody. T-DM1 combines the cancer cell killing drug DM1 with the monoclonal antibody trastuzumab, which binds selectively to the HER2 growth signal receptor and blocks the growth signal.
Krop explains that the antibody component of the hybrid agent binds to the HER2 protein on cancerous tumor cells and delivers the drug (DM1) selectively to them without harming normal cells, allowing higher doses of the chemotherapy drug to be administered. The antibody also continues to block HER2 growth signals, for a combined effect.
According to Krop, cancer cells often develop resistance to chemotherapy drugs that are effective against HER2-positive cancer otherwise, such as Trastuzumab, developed by Genentech and sold under the name Herceptin.
Krop claims his study is the first with a test population of women whose metastatic HER2-positive breast cancer had progressed following treatment with other standard chemotherapy agents. The women had metastatic breast cancer for an average of three years and had received up to seven different cancer-fighting drugs.
The new drug was generally well-tolerated and side effects experienced by the patients -- including nausea, fatigue and lowered platelet counts -- were usually mild, reports Krop.
Background information in the Dana-Farber Cancer Institute's press release states that T-DM1's effectiveness, compared with other combined therapies, is already being tested in Phase 3 clinical trials.