Targeted Therapies: Four Drugs for Her2 Positive Tumors
In 1985 scientists discovered a gene that makes cells produce too much of a protein called human epidermal growth factor receptor 2 (Her2) and found that this gene was associated with aggressive breast cancer tumors. Thirteen years later in 1998, the FDA approved a new drug called trastuzumab (Herceptin) for people whose breast cancers overexpressed the Her2 protein. Herceptin was a miracle drug for the 20-25 per cent subset of breast cancer patients who are positive for Her2 overexpression.
I had been following the Herceptin clinical trials since my own diagnosis with Her2 positive inflammatory breast cancer (IBC) in April of 1998, and I was disappointed when my oncologist did not want to put me on it after its approval in the fall. The initial approval was just for Stage IV patients, and I was at Stage IIIB. "We'll save the Herceptin for if you progress," she said.
Although the FDA would not officially approve Herceptin for non-metastatic breast cancer until 2006, it was not long before my Her2 positive IBC friends' doctors were putting them on it off label or urging them to participate in the trials for its expanded use. While Herceptin worked for many people, some people had heart problems that contraindicated its use, and other people found that it lost its effectiveness for them over time.
Herceptin was the first of a new type of drugs that worked not by killing cancer cells but by targeting the pathways that allow them to grow. Unlike chemotherapy drugs which kill all kinds of cells, the targeted therapies usually have fewer side effects because their action in the body is more limited. Chemotherapy is still part of the treatment, but Herceptin makes the chemotherapy work better. The insights that researchers gained into stopping cancer growth by blocking the pathways that allowed cancer cells to flourish led them to investigate other targeted therapies.
In 2007, a year after Herceptin won FDA approval for non-metastatic disease, lapatinib (Tykerb) was approved. Then in 2012, pertuzumab (Perjeta) was added to the list of drugs available for metastatic breast cancer patients with Her2 positive tumors. Now this spring, one more targeted therapy brings hope to metastatic patients. This one was called TDM-1 in the clinical trials. Its trade name is Kadcyla.
My friends in the metastatic breast cancer community are thrilled with the release of this new drug. Several who were in the trials for it had fantastic results, so others whose disease has continued to progress on the older drugs are anxious to give it a try. How well it will work on larger groups of people in the long term has yet to be seen. I remember how excited people were about Avastin several years ago and how disappointed they were when it proved less effective than hoped.
Another new twist in the targeted therapy story is that Herceptin may work on tumors that have tested Her2 negative. Max S. Wicha, professor of oncology and director of the University of Michigan Comprehensive Cancer Center and colleagues found breast cancer stem cells comprise only a small portion of cells within a breast tumor, but these cells can be Her2 positive and affect how aggressively a tumor grows. The researchers want to see if Herceptin can stop tumor growth even for women whose proportion of Her2 positive cells is too small to label the entire tumor Her2 positive. They plan a clinical trial to check out this idea.
What I find exciting about the targeted therapy story is how scientists learn from each new breakthrough. It was 13 years from identifying the Her2 gene until Herceptin was approved from that research; another eight years until Herceptin was approved for more general use. Then one year later, Tykerb, came out; followed by Perjeta five years later and Kadcyla the next year. Of course, each of these drugs has been years in research and development, but it seems that once scientists find a new way to fight disease, the next steps are easier.
What does all this research mean for you? First, you need to be sure your doctor checks even small tumors to see if they are Her2 positive. If you have more than one tumor, they may not have the same profile, so each needs checking. If you are Her2 positive, then your doctor has probably already discussed Herceptin with you, but if not, be sure to ask. There are some reasons your doctor might not want you to have it, especially if you have a history of heart problems, but go over the risks and benefits with your doctor as they apply specifically to you.
Second, if you have metastatic disease that is progressing, ask about the newer targeted therapies, especially about whether Kadcyla might be right for you. Again there are contraindications including pregnancy, liver, and heart problems, and your oncologist can help you sort out the pros and cons.
Third, whatever your connection to cancer take hope from the advances in cancer treatments. Sometimes it seems like the progress is slow, but the new researchers build on the accomplishments of those who came before them. Be generous in supporting the kind of basic research that eventually leads to treatments.
Azvolinsky, Anna. Trastuzumab may have role in HER2-Negative Breast Cancer Treatment. Cancer Network. March 12, 2013. Accessed from http://www.cancernetwork.com/her2-positive-breast-cancer April 26, 2013.
Davidson, Nancy E. Fifteen years of Anti-HER2 therapy. Cancer Network. March 12, 2013. Accessed from http://www.cancernetwork.com/her2-positive-breast-cancer/content/article/10165/2132153 April 26, 2013.