Researchers to test two targeted therapies together to treat early HER2-positive breast cancer

Monday, April 02, 2007

JACKSONVILLE, Fla. — Combining two drugs targeted against HER2-positive breast cancer could offer patients more benefit than just using one, says a Mayo Clinic researcher who is set to test the concept in the first major clinical study of its kind.

Edith Perez, M.D., director of Mayo Clinic's Breast Clinic in Jacksonville, Fla., is leading a national clinical trial with 109 participants that will look at the safety and benefit of adding lapatinib (Tykerb) to trastuzumab (Herceptin) for the treatment of early- stage HER2-positive breast cancer. The study, which opened March 16, 2007, is recruiting patients.

"Worldwide, no more than 100 patients have been tested with this combination treatment, so we are pleased that we now offer a comprehensive study in the United States to assess the possible benefit of this therapy," says Perez. She will lead a consortium of 35 investigators who will enroll 109 participants at up to 100 different cancer treatment centers across the country.

"This clinical trial is one more example of taking the biology of breast cancer into the clinic," she says. "We are finding that the best way to treat a cancer is to understand the biological characteristics of the cancer and then use therapies directed at those specific biological or molecular abnormalities."

One drug is approved for early- and advanced-stage HER2-positive breast cancer; the other for advanced

Between 25 percent and 30 percent of breast cancer is HER2-positive, meaning that growth-promoting HER2 proteins are overly abundant on the outside membrane of the cancer cells, promoting an aggressive disease. Trastuzumab is a monoclonal antibody, delivered by intravenous injection, which helps shut down the activity of these proteins by binding on to the part of the protein that sticks up from the cell surface. In 1998, the Food and Drug Administration (FDA) approved trastuzumab for use in advanced HER2-positive breast cancer; and in 2006, trastuzumab was approved for use in early-stage HER2-positive breast cancer. One of the studies that showed its benefit for early-stage breast cancer was conducted by Perez, who found that trastuzumab cut cancer recurrence by 52 percent, compared to standard therapy.

Lapatinib, which is given as a pill, is designed to block HER2-protein activity from inside a cell, and it also shuts down other pro-cancer molecules as well, Perez says. An international clinical trial testing lapatinib in patients with advanced HER2-positive breast cancer was so successful that the trial was stopped early so that all patients in the study could use the drug. In the study, the patients with advanced HER2-positive breast cancer whose tumor(s) progressed after treatment with trastuzumab either received chemotherapy alone or a combination of lapatinib plus chemotherapy. The combination delayed the progression of cancer for nearly twice as long as those who received only chemotherapy. The FDA approved lapatinib for use in advanced HER2-postive breast cancer March 2007.

Combining both therapies "might work synergistically, attacking HER2 from the inside and the outside of the cancer cell," Perez says. She also has reviewed multiple lapatinib studies, testing whether it can impact heart activity in the same way that trastuzumab can. Perez reported in June 2006 that of the 2,812 patients who have participated in various international lapatinib clinical studies, only 37 patients (1.3 percent) experienced some decreased cardiac functioning, and that these problems were usually clinically reversible. The study of cardiac tolerability to lapatinib has continued, and now includes more than 3,500 patients from around the world, and the "rate of cardiac events remains about 1 percent, which is very low," she says.

A pill of lapatinib a day for a year

All patients who enroll in this new study must have newly diagnosed, untreated, early-stage HER2-positive breast cancer. The usual treatment protocol will be followed, except that lapatinib will be added.

Specifically, after surgery to remove their tumors, patients will receive two chemotherapy drugs intravenously, doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) for two or three months. This will be followed by treatment with another chemotherapy drug, paclitaxel (Taxol), and trastuzumab every week for three months. The study drug, lapatinib, will be added to this phase of treatment.

Then, patients will continue to receive trastuzumab treatments every three weeks and will take lapatinib every day for the next nine months. Tests to check heart function will be taken before treatment begins, as well as during and after the study.

Perez and the clinical investigators will collaborate with research scientists and cardiologists at Mayo Clinic and Massachusetts General Hospital to examine blood profiles of participants, Perez says. "We will be looking for any markers that could predict which patients might experience cardiac toxicity," she adds. "This is a new comprehensive way to evaluate novel technologies and blood markers that may help us predict which patients may eventually develop diminution of cardiac function."

"We are excited about this study because of the hope that it will offer our patients the most benefit possible, given a therapy already known to save lives and one that is showing great promise," Perez says.

For more information about this clinical study, please visit http://clinicaltrials.mayo.edu, call the Cancer Trials Referral Office at (507) 538-7623 or e-mail cancerclinicaltrials@mayo.edu. Information about RC0639 also is available via the National Institutes of Health Web site, www.clinicaltrials.gov.

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To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. MayoClinic.com is available as a resource for your health stories.