Trastuzumab-DM1 - a 'smart bomb' for breast cancer treatment

Sarah Cannon Research Institute (SCRI) investigators have found that "smart bomb" therapies are effective in treating breast cancer patients while minimizing side effects.

Howard A. Burris III, M.D., SCRI's chief medical officer, is presenting interim Phase II clinical trial results of a drug named Trastuzumab-DM1 (T-DM1), a novel antibody drug conjugate, at the American Society of Clinical Oncology's Breast Cancer Symposium in Washington, D.C.

T-DM1 is built from the widely used antibody Herceptin. T-DM1 combines Herceptin's HER2 blocking activity with a targeted intracellular delivery of a potent anti-microtubule agent directly into HER2-positive breast cancer cells. In 20 percent of breast cancer cases, the patient's cancer has too much of the HER2 protein, which makes the cancer cells grow and divide more quickly. T-DM1 is designed to focus delivery of treatment to HER2-positive cancer cells and limit delivery to surrounding healthy tissue.

Dr. Burris and his team were the first oncologists to treat patients with T-DM1 in December 2006. Minimal toxicities have been observed in the trial to date.

"Physicians call it a 'smart bomb' because it's designed to hit the target cancerous cells with minimal collateral damage to its neighboring non-cancerous cells," Dr. Burris said.

Thirty-one patients with HER2-positive metastatic breast cancer whose tumors had progressed on prior HER2-directed therapy in the trial received 3.6 mg/kg of T-DM1 by IV every three weeks. The interim findings of the Phase II study include evidence of tumor shrinkage in some patients.

Murfreesboro, Tenn. resident Nancy Fann, 64, had been on at least three chemotherapy treatments since cancer had spread from her lung to her liver and breast, but the tumors kept coming back. In May 2007 she enrolled in the T-DM1 clinical trial.

"The tumors are considerably smaller than they were to begin with," Fann said. "This drug doesn't seem to affect me as much as some of the others I've been on. I don't get sick and I haven't lost my hair."

Denise A. Yardley, M.D., SCRI's director of breast cancer research, also is presenting her research on two trials today at noon. Both trials focus on targeted therapies for patients with HER2-positive metastatic breast cancer.

One trial shows preliminary results from a Phase II trial of a combination of Herceptin and the chemotherapy drug oxaliplatin. Twenty-one patients have enrolled in the trial so far, and early results show the treatment is active with little to no significant side effects seen to date.

The other trial focuses on a combination treatment of Avastin and the chemotherapy drug docetaxel for early-stage, metastatic breast cancer. A cohort of patients with HER2-positive disease also receives Herceptin as part of the study. Data for the first 138 patients enrolled indicate the treatment is reasonably well-tolerated without unexpected side effects.

"As knowledge about tumors and tumor biology grows, we're learning that all breast cancers are not identical," Dr. Yardley said. "These smart new drugs help target treatment specific to certain types of tumors, causing less damage to healthy cells and reducing side effects."

SCRI is one of the largest clinical research programs in the nation, conducting community-based clinical trials in oncology, cardiology, gastroenterology and other therapeutic areas through affiliations with a network of nearly 500 physicians in 24 states. Additionally, SCRI offers management, regulatory and other research support services to drug development sponsors and strategic investigator sites across the country.

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