Experimental Drug T-DM1 Clinical Trials Encouraging Against Aggressive Breast Cancer

Investigational drug linked to Herceptin promising in clinical trials.

June 3, 2012— -- For Bridget Spence, graduation from college was a short-lived joy. Just one week after receiving her degree, a medical diagnosis sent her reeling.

"I was diagnosed with stage 4 breast cancer in 2005. Cancer was in my lymph nodes, liver and breast at the time of my diagnosis," she told ABC News.

She had HER2-positive breast cancer, a particularly aggressive form of the disease. For four years, her cancer progressed, and a combination of drugs kept it stable for a while.

But about a year ago, her cancer started growing again, and she wasn't sure what she would do. That's when her doctors at Dana Farber Cancer Institute told her about a trial of an experimental drug, called T-DM1, designed to target and attack cancer cells in HER2-positive breast cancer patients.

While other drugs couldn't shrink Spence's cancer, she said T-DM1 did, and kept it at bay for nine months.

She also didn't have the debilitating side effects characteristic of other cancer drugs.

"The best part is it was very tolerable," she said. "I've lived a completely normal life. I worked full-time, was able to buy a house and walked 60 miles in three days while on the drug."

Spence said she felt "lucky to be in the trial," and the researchers who studied the drug in a clinical trial were also encouraged by its effects.

They presented their study findings at the annual meeting of the American Society for Clinical Oncology in Chicago this weekend.

T-DM1 is a combination of Herceptin, a drug commonly used to treat HER2-positive breast cancer, and an experimental drug called emtansine, or DM-1.

They found that the drug kept patients free of disease for longer than a standard chemotherapy regimen.

About 1,000 patients with HER2-positive breast cancer from several countries were enrolled in a phase 3 clinical trial of T-DM1. One group of patients received T-DM1 and the other group received two standard chemotherapy drugs.

The T-DM1 patients remained cancer-free for 9.6 months -- the progression-free survival -- while the standard treatment group were cancer-free for 6.4 months.

"What we saw was that close to 18 more out of 100 women were alive after two years because they got the new drug compared to older form of treatment," said Dr. Kimberly Blackwell, the study's lead investigator and an oncologist at Duke University Medical Center.

Progression-free survival is the time that elapses between the start of a treatment and the time the cancer gets worse. T-DM1, however, did not improve overall survival.

There is considerable debate among clinicians about using progression-free survival to measure a drug's effectiveness, but Dr. Sara Hurvitz, a study investigator and director of the Breast Oncology Program at UCLA's Jonsson Comprehensive Cancer Center said it can give an early indication of how well a drug is working.

The patients who received T-DM1 also experienced fewer side effects, which is also a very important finding.

"This is a very nice molecule that targets HER2-positive breast cancer," Hurvitz said. "Herceptin is linked in a very stable fashion to a highly cytotoxic chemotherapy drug, which is highly potent."

There have been early drug trials evaluating the effects of DM1 alone, but Hurvitz said the drug was too toxic, so far unlike the combination agent T-DM1.

"This is very unusual for cancer drug trials. In many drug trials with improved outcomes, we see worse effects, but in this trial, we use two drugs, see better outcomes and have better quality of life measures," said Blackwell.

With T-DM1, she added, women didn't even lose their hair, and experienced far fewer other side effects.

"This can really have an impact on patient's lives," she said.

Because of the linkage between the drugs, the chemotherapy is not activated until T-DM-1 gets inside the cancer cells, she explained, leading to fewer side effects.

Not a Cure, But a Step Forward

For a notoriously aggressive cancer such as HER2-positive breast cancer, the study findings are encouraging.

"We're getting responses that are looking better than at least one conventional choice and a toxicity profile that is better," said Dr. Clifford Hudis, chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center, who was not involved with the study. "It may not be the cure for this cancer and may represent one chapter in a fairly long book for people who have metastatic breast cancer, but it's a new and additional option."

"We don't have evidence of a significant improvement in overall survival so we're not curing people, but if you're going to be treated, this has real benefits."

Dr. Eric Winer, director of the breast oncology center at Dana Farber Cancer Institute, said the effectiveness of the drug, paired with its low side effect profile, could be a boon for many patients.

"It has been shown to be effective when other standard treatments have stopped working, and it has great promise as a drug to be used earlier in the course of the disease," Winer said. "I have been using the drug on clinical trials for six years, and we have patients who have been on it for two years, three years... Not [for] everyone, butfor some it is amazing."

For Spence, the new drug meant she could live a normal life. Although her cancer once again started to progress, she is grateful for the nine months it didn't.

"It gave me more time with my husband," she said. "We need more options for women with stage 4 breast cancer, and this is a wonderful option. It gives the opportunity to be normal women and mothers and wives."