Women with an aggressive type of advanced breast cancer can live significantly longer without their disease getting worse if they are treated with an experimental armed antibody drug from Roche, researchers said on Sunday.
Data from a mid-stage clinical trial of the new combination drug, trastuzumab emtansine (T-DM1), in HER2-positive breast cancer found patients given T-DM1 had a 41 percent improvement in the time without their breast cancer worsening compared with those given trastuzumab, or Herceptin, plus chemotherapy.
Side effects were also significantly reduced in the T-DM1 group, a factor that was particularly important and very clinically meaningful, said the study's lead investigator Sara Hurvitz, since far fewer T-DM1 patients opted to stop treatment during the phase II trial.
The results are a boost for the medicine, which the Swiss drugmaker Roche has been developing with ImmunoGen as a successor to its blockbuster Herceptin. Herceptin had sales of more than $5 billion in 2010.
These provocative Phase II data illustrate that first-line treatment with T-DM1 provides a longer time for patients to live without cancer progression and with fewer side effects than standard chemotherapy plus trastuzumab, said Hurvitz, director of the breast oncology program at University of California, Los Angeles, who presented her findings at the European Multidisciplinary Cancer Congress (EMCC) in Stockholm.
In the trial, which involved 137 patients who had not previously had chemotherapy or HER2-targeted therapy, those on T-DM1 had an average 14.2 months without the disease worsening versus 9.2 months for those given Herceptin plus chemotherapy.
The proportion of women who stopped treatment due to side-effects was 7.2 percent in the T-DM1 arm compared with 28.8 percent in the standard therapy arm of the study.
MAGIC LINK IN ARMED ANTIBODY
T-DM1 is a new kind of so-called armed antibody drug that can carry a cell-killing payload into cancer cells.
It combines trastuzumab, an antibody and the active ingredient in Herceptin, with the agent DM1 -- a derivative of an extremely powerful type of chemotherapy called maytansine.
Maytansine was a chemotherapy that was being developed in the 1980s, but it was so toxic that they shelved it, Hurvitz told reporters during an EMCC briefing. So what they've done now is to figure out how to link it to the trastuzumab -- so that it is not activated until it reaches the cancer cell.
The magic is in the link, she said. The whole thing is internalized within the cell. It's actually quite unique.
The fact the drug delivers its toxic payload directly into cells is also thought to be key to why it causes fewer side effects like hair loss and low white blood cell counts.
Trial data showed that only 4 percent of patients in the T-DM1 treatment group suffered hair loss, compared with 67 percent of those in the standard treatment group.
As well as having fewer unpleasant side effects, Roche believes its new drug also offers greater convenience, since it is one drug and eliminates the need to administer chemotherapy.
Commercially, it should help protect Roche's breast cancer franchise, since Herceptin could be exposed to so-called biosimilar generic competition in Europe from around 2015.
Consensus forecasts from Thomson Reuters Pharma show analysts see T-DM1 generating sales of $694 million by 2016.
It also keeps Roche in the breast cancer innovation race in the face of newer medicines that aim to rival Herceptin, like British drugmaker GlaxoSmithKline's Tykerb.
Oncology experts described Hurvitz's study as important and said the results were promising but would need to built upon by further late-stage studies.
Roche is conducting several Phase III trials of T-DM1 and Hurvitz said the results from one of these -- looking at T-DM1 versus GSK's Tykerb plus Xeloda, another type of chemotherapy also made by Roche -- are expected in the first half of 2012.
Hurvitz said that if those data are positive, Roche will then apply to U.S. drug regulators for a license for T-DM1.