Doctors today will unveil the results of the first large trial of a new kind of "precision medicine" against breast cancer: a drug combination designed to act like a smart bomb, which delivers its payload directly to tumor cells while reducing collateral damage to the rest of the body.
The experimental drug, T-DM1, doesn't cure anyone.
But it attacks breast cancer in a whole new way - one that may be useful against a variety of other tumors - and appears significantly better at controlling cancer than the current standard of care, says Kimberly Blackwell, who presents her findings today in Chicago at the annual meeting of the American Society of Clinical Oncology.
T-DMI combines the drug Herceptin, a man-made antibody, with an old-fashioned chemotherapy drug called emtansine, Blackwell says.
Herceptin, approved in 1998, was designed to block growth signals from a protein found almost exclusively on cancer cells called HER2, says Sandra Horning, global head of development at Genentech, the drug's developer. Herceptin homes in on HER2 proteins, binds to them and blocks them from transmitting run-away growth signals. To create T-DM1, scientists attached chemotherapy molecules to Herceptin, hanging them like ornaments on a Christmas tree. When T-DM1 is infused into the body, Herceptin zeroes in on HER2 proteins and releases its "payload" of toxin directly at the cancer cell. The toxin then enters the cancer cell and kills it, Horning says.
The T-DMI stats
An experimental breast cancer drug, T-DM1, was more effective and produced fewer side effects than the standard approved therapy, which combines the pills Xeloda and Tykerb, researchers said Sunday.
New therapy: T-DM1/ Standard care: Xeloda + Tykerb
Percent of patients alive at 1 year 85% /77%
Percent of patients alive at 2 years 65% /48%
Percent of patients whose tumors shrank at least 30%: 44% /31%
Percent of patients who developed serious side effects 41%/ 57%
Percent of patients who had to reduce medication dose due to side effects: 16% Reduced Xeloda dose: 53%/Reduced Tykerb dose: 27%
Source: American Society of Clinical Oncology
That's a big change from traditional chemo, in which controlled doses of poison are infused into the bloodstream. While chemo kills cancer cells, it also kills healthy tissues, too, often causing grueling side effects of nausea, vomiting and fatigue, as well as life-threatening infections.
Doctors tested T-DM1 in a study of nearly 1,000 women with advanced cancers who had been on Herceptin, but who are no longer benefitting from it. All of the women had breast cancers that make lots of HER2.
T-DM1 kept these women's cancers in check for 9.6 months, about three months longer than standard therapy, which combines the anti-cancer pills Tykerb and Xeloda, according to the study.
Doctors also noticed a trend suggesting that women randomly assigned to take T-DM1 live longer, as well. After two years, 65% of those on T-DM1 were alive, compared to 48% of those on Tykerb and Xeloda.
"It's a major advance," says Jo Anne Zujewski, a breast cancer researcher at the National Cancer Institute, who was not involved in the study. "I'm excited for women."
People should be cautious about overestimating T-DM1's survival advantage, because, statistically, it's possible that those findings could be due to chance, Horning says. As researchers continue to monitor the women's progress, doctors will get a better sense if T-DM1 really improves survival.
Louis Weiner, director of the Georgetown Lombardi Comprehensive Cancer Center in Washington, says breast cancer patients are in great need of new treatment options. While Herceptin has helped many women, most breast cancer patients with advanced disease eventually relapse, he says.
Breast cancer patient Shirley Mertz, 65, says she's also glad to see women with another option. She knows women who don't respond well to standard treatments, or who find the side effects intolerable, says Mertz, who lives in the Chicago area and takes Herceptin for advanced breast cancer that recurred in spite of an earlier mastectomy.
T-DM1 has generated enormous excitement among breast cancer patients, says Mertz, a board member of an advocacy group called the Metastatic Breast Cancer Network. Women's main frustration, she says, is that it's not yet widely available. Because T-DM1 is experimental, it's available only through clinical trials, Horning says. Genentech plans to apply for Food and Drug Administration approval later this year. Genentech, which plans to test T-DM1 in early breast cancer, has not yet announced how much T-DM1 will cost. Herceptin alone, in the doses currently used to treat breast cancer, costs thousands of dollars a month.
Blackwell says she's pleased that women on T-DM1 almost never suffer from the nausea, diarrhea or hair loss that's typical of chemo. In the study, 41% of those taking T-DM1 had serious side effects, compared to 57% of those on standard therapy.
The drug used in T-DM1, emtansine, is an incredibly potent poison, Blackwell says. Early tests showed it was far too toxic to be used in people, at least when given in a typical intravenous infusion. But doctors can administer very strong doses by targeting its poison directly at cancer cells, she says.
Zujewski says she hopes this technique will catch on.
Genentech is testing eight similar antibody-drug combinations in the clinic, with 25 in its research pipeline, Horning says.
"It does lead me to believe that more molecules are going to be developed that will work this way," she says.
Weiner notes that doctors are already using other man-made antibodies to fight cancer, including the drugs Erbitux and Rituxan. These drugs could find additional uses, if researchers can successfully attach chemo molecules to them, too, he says.
"We talk a lot about developing a cancer bomb," Blackwell says. "This is an example of delivering that bomb to the cancer, not the patient."