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Antibody-guided drug shows encouraging activity in metastatic breast cancer
Date:12/12/2009

SAN ANTONIO, TXA new antibody-drug compound shrank or halted the growth of metastatic breast tumors in almost half of a group of patients whose HER2-positive cancer had become resistant to standard therapies, according to early data from a multicenter Phase 2 clinical trial led by a Dana-Farber Cancer Institute researcher.

The findings will be presented at the 32nd annual CTRC-AACR San Antonio Breast Cancer Symposium on Saturday, Dec. 12 (Abstract 710, Henry B. Gonzalez Convention Center, Exhibit Hall B, 7-9 a.m. CT).

Ian Krop, MD, PhD, principal investigator of the study, will report that the hybrid agent, called T-DM1, shrank tumors by 30 percent or more in 40 percent of women with confirmed HER2-positive cancers. Another 13 percent had stable disease for at least six months, for a total clinical benefit rate of approximately 53 percent. The median time before the disease progressed was 7.3 months, including both responders and non-responders. Patients received T-DM1 as long as it was effective and well-tolerated. A total of 110 women were enrolled in the study.

T-DM1 is comprised of the cell-killing drug DM1 and is chemically linked to the monoclonal antibody trastuzumab, which selectively binds to the HER2 growth signal receptor, which is highly overexpressed in HER2-positive breast tumors. Approximately 20 percent of breast cancers are HER2-postive.

Trastuzumab, developed by Genentech and sold under the name Herceptin, has markedly improved the treatment of HER2-positive cancer, but resistance to trastuzumab is a significant problem.

"The antibody binds to the HER2 protein on tumor cells and delivers the drug (DM1) selectively to them but not to normal cells," Krop explained. "This allows us to deliver high doses of the chemotherapy directly to tumor cells. And at the same time, the antibody continues to block the HER2 growth signals."

Krop said that one of the unique features of the study is that i
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-4090
Dana-Farber Cancer Institute
Source:Eurekalert

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