Novel targeted therapies on the horizon for breast cancer could more effectively change the way the disease is treated, said Dr. Aditya Bardia, attending physician and breast oncologist at the Massachusetts General Hospital (MGH) Cancer Center in Boston.
“The field of breast cancer therapeutics is changing rapidly, and in the next few years we could see a revolution in breast cancer management,” he said.
What oncologists and cancer researchers are increasingly recognizing is that breast cancer is not one disease. The keys are to identify the mutations that drive an individual cancer in order to inhibit those targets successfully with targeted therapies, alone or in combination, he said. He cites the HER2 story as an example. HER2 is a receptor that occurs in about 20 percent of breast cancers.
“In general, HER-2+ tumors have a worse prognosis. However, with the advent of an antibody against HER-2, trastuzumab (Herceptin), the landscape has changed and no longer are these tumors considered to have a worse prognosis,” Bardia said. “In fact, we now have three FDA-approved targeted therapies against HER2+ disease, and a number of novel therapies are in clinical trials.”
An exciting new drug on the horizon for HER2+ breast cancer is T-DM1, he said. DM-1 is a chemotherapy agent that’s very potent, and if given alone, is very toxic. However, in T-DM1 the chemotherapy, DM-1, is linked to the HER-2 antibody, trastuzumab, which binds only to the cancer cells which overexpress HER2. As such, the normal cells in the body that do not have HER2 overexpression are spared.
“It’s a ‘smart bomb’ in that it effectively targets the cancer cells but does not affect the normal cells, in general,” Bardia said.
The results of a large phase III clinical trial of T-DM1 were presented at the national meeting of the American Society of Clinical Oncology this year and the drug application has been submitted to the FDA with a decision expected in early 2013.
Targeted therapies are more effective because they could potentially be tailored to the genetic profile of the tumor, rather than the concept of one size fits all, said Bardia. However, the field is not without its challenges.
Foremost, accurate identification of key “driver” mutations is crucial as not all mutations are the same, and like any therapy, over time resistance to targeted therapies can emerge by activation of parallel pathways, he said. Combination of targeted therapies can potentially overcome treatment resistance by co-targeting important pathways in the cancer cell.
For example, results from a large phase-3 clinical trial were published this year in the New England Journal of Medicine in which an anti-hormone therapy called exemestane (an FDA-approved medication for treatment of hormone-receptor-positive breast cancer) was combined with everolimus (a mTOR inhibitor), to overcome treatment resistance to endocrine therapy. The result was a near tripling of disease-free survival for women with metastatic hormone-receptor-positive breast cancer.
“Rational combination of the mTOR inhibitor with anti-hormone therapy is a major advance in the treatment of hormone-receptor-positive cancer, and various exciting targeted therapy combinations are in clinical development” Bardia said.
“It’s not difficult to envision a future when there will be no chemotherapy for breast cancer and we are just able to use targeted therapies based on the individual’s profile and spare an individual from the side effects of chemotherapy,” Bardia said.