In a key clinical trial with 1,000 women who had advanced breast cancer, the efficacy of an experimental treatment for breast cancer has been examined in some detail. This breast cancer treatment is one of the first “smart bomb” treatments for breast cancer.
This treatment uses a drug to deliver a toxic payload to tumor cells that also leaves the healthy cells alone. In this treatment, woman with advanced disease this experimental “smart bomb” treatment extended the lives of these sick women by several months, and during this time, the women lived without their cancer getting worse. After two years, 65 percent of women who received this treatment were still alive versus 47 percent of those in a comparison group who were given two standard cancer drugs. The developers of this treatment plan to report on it at a cancer conference in Chicago.
“The absolute difference is greater than one year in how long these people live,” said the study’s leader, Dr. Kimberly Blackwell of Duke University. “This is a major step forward.”
How does this treatment work? It builds on the cancer drug, Herceptin. Herceptin was developed as a gene-targeted therapy for breast cancer. In fact, it was the first gene-targeted treatment ever developed. Herceptin is used for about 20 percent of patients whose tumors overproduce a certain protein. Herceptin is the trade name for the drug trastuzumab, and this drug is a monoclonal antibody. Trastuzumab binds to a protein called “human epidermal growth factor receptor 2” or Her2. Her2 has several other names (Neu, ErbB2, CD340 or p185), but whatever you call it, Her2 binds a small protein called epidermal growth factor (EGF). The binding of EGF to Her2 sets a series of events into action inside the cell that causes it to grow and divide vigorously.
Her2 is overexpressed in breast cancer cells and the excessive signaling to the cell interior drives the breast cancer cells to grow faster and faster. Trastuzumab binds to Her2 and shuts the signaling that emanates from it down. Trastazumab is used as part of a treatment regimen that includes drugs like Adriamycin® (doxorubicin), Cytoxan® (cyclophosphamide), and either Taxol® (paclitaxel) or Taxotere® (docetaxel). Such a treatment course is known as “AC→TH.” Other treatment regimens include Herceptin with Taxotere and Paraplatin® (carboplatin). This treatment course is known as “TCH.”
In this “smart bomb” treatment, researchers linked trastuzumab to a toxin that kills cells once it gets inside them. This new drug is called T-DM1, the “smart bomb.” Herceptin binds the toxin to the cancer cells, and the toxin provides the coup de gras for the cancer cell. Doctors tested T-DM1 in 991 women who suffered from breast cancer that had spread throughout their body and was getting worse despite treatments with available chemotherapy and ordinary Herceptin. The women in this study were given T-DM1 infusions every three weeks or infusions of standard breast cancer treatment drugs (Xeloda plus daily Tykerb pills). The median time until cancer worsened was nearly 10 months in the women given T-DM1, in comparison to just over 6 months for those who received the other treatments. According to Blackwell, this is about the same magnitude of benefit initially seen with Herceptin, which later proved to improve overall survival
Even more interestingly, T-DM1 caused fewer side effects than the other drugs. Unfortunately, some women on T-DM1 showed had signs of liver damage and poor blood clotting, but most patients did not show the usual problems of chemotherapy. According the Blackwell, “People don’t lose their hair, they don’t throw up. They don’t need nausea medicines, they don’t need transfusions.”
Dr. Michael Link, a pediatric cancer specialist at Stanford University who is president of the American Society of Clinical Oncology, the group hosting the Chicago conference where the results were being presented, said “The data are pretty compelling. It’s sort of a smart bomb kind of therapy, a poison delivered to the tumor … and not a lot of other collateral damage to other organs.”
Dr. Louis Weiner, director of Georgetown Lombardi Comprehensive Cancer Center, said the results strongly suggest T-DM1 improves survival, since it delivers more drug directly to tumors with less side effects. This is a clear advance over other chemotherapeutic drugs.
Denise Davis, 51, a customer service representative at a propane company, was diagnosed three years ago with breast cancer that had spread to her liver and bones. Since February of last year, the Lynchburg, Va., woman has made the two-hour trip to Duke in Durham, N.C., every three weeks to get infusions of T-DM1. Davis called T-DM1 “Herceptin-plus.” Cancer scans every six weeks show her tumors are either shrinking or stable. Davis concluded, “Right now, I’m feeling pretty good about it. The only way I’d feel a little better is if it took care of everything, but I’ll take what I can get.”
Genentech, part of the Swiss company Roche, plans to seek approval later this year to sell the drug in Europe and the United States. Another company, ImmunoGen Inc., made the technology that combined the two drugs. Genentech says the price of T-DM1 has not been determined. Herceptin costs more than $4,000 a month plus whatever doctors charge to infuse it. Herceptin’s U.S. patent will not expire until 2019.