- What is HER2?
- How Do Physicians Test for HER2?
- What is Herceptin?
- How Does Herceptin Work?
- Who is a Candidate for Herceptin?
- What Have Clinical Trials with Herceptin Shown?
- What are the Side Effects of Herceptin?
- What is Tykerb?
- What Have Clinical Trials with Tykerb Shown?
- What are the Side Effects of Tykerb?
- Additional Resources and References
HER2 human epidermal growth factor receptor 2) is a protein found on the surface of breast cancer cells. Some breast cancer patients have extra copies of HER2 that can be associated with more aggressive or treatment-resistant cancers. Herceptin and Tykerb are two drugs approved by the U.S. Food and Drug Administration (FDA) that may be used to treat breast cancer in these breast cancer patients, in combination with other breast cancer treatments. Tykerb is typically used in patients who have already been treated with Herceptin.
HER2 testing is becoming more common. Knowing the results of the test can help physicians and patients determine which treatment options are most likely to be effective. HER2 testing is performed on cancer cells that have been removed during breast biopsy or breast cancer surgery. Testing may also be performed on cells from a breast tissue sample that has been stored from a previous biopsy (many laboratories keep tissue samples for years after the initial biopsy or surgery).
Testing for HER2 protein over-expression involves staining the tissue sample with a specific solution in a pathology laboratory. The pathologist then examines the cells within the tissue sample, checking for highlighted areas where high levels of HER2 over-expression are present. Depending on the level of staining, the patient’s cancer may be classified as HER2 positive or HER2 negative.
Herceptin (generic name, trastuzumab) is a drug used to treat some women with advanced breast cancer whose cancer has spread to other areas of the body. Approved for use by the U.S. Food and Drug Administration (FDA) in September 1998, Herceptin has shown great promise in increasing patient survival time and reducing the number of deaths from advanced breast cancer. Clinical trials are also investigating whether Herceptin is helpful for women with early-stage breast cancers.
According to Genentech, the manufacturer of Herceptin, approximately 35,000 women have been given Herceptin since it first received FDA approval. However, not all breast cancer patients are candidates for Herceptin. The drug only appears to work for women whose breast cancer cells carry extra copies of a protein called HER2 (also written HER2/neu).
The drug Herceptin is a monoclonal antibody engineered through biotechnology. It targets breast cancer cells that have too many copies of the HER2 protein. After it has identified which cells over-express the HER2 protein, Herceptin attaches itself to the HER2 protein receptors on the surface of these cells. By binding to the cells, Herceptin slows the growth and spread of tumors that have an overabundance of HER2. Many experts believe that Herceptin represents the future direction of breast cancer drugs in that it targets a particular protein of the cancer cell and prevents it from carrying out its action, similar to the new leukemia drug, Gleevec. Herceptin is given intravenously (through the vein) in an outpatient clinical setting.
Currently, Herceptin is FDA approved, in combination with the drug paclitaxel, to treat women with advanced, HER2 positive breast cancers.
Herceptin was shown to slow the growth and spread of cancerous tumors in a number of clinical trials prior to FDA approval in 1998. In some cases, cancerous tumors completely disappeared in patients taking Herceptin. In one clinical trial, 469 patients with metastatic cancer who over-expressed HER2 received either Herceptin with chemotherapy or Herceptin alone. Among the 235 women who received Herceptin with chemotherapy, researchers saw significantly less rapid tumor growth. Many tumors were reduced by 50% or more in size, and the one-year cancer survival rate was higher compared to women who underwent chemotherapy alone (79% versus 68%).
Studies conducted after Herceptin received FDA approval continue to show its effectiveness in treating advanced breast cancer patients who carry extra copies of the HER2 gene. In 2005, the National Cancer Institute announced the results of two clinical trials of Herceptin which showed that the drug can offer potentially life-saving treatment to women with HER2 positive breast cancer. In the trials, HER2 positive breast cancer patients who received standard chemotherapy (with the drugs doxorubicin and cyclophosphamide) followed by treatment with the drug paclitaxel and Herceptin had a 52% decrease in the recurrence of disease after treatment, compared to women who did not receive Herceptin.
"This is a major advance for many thousands of women with breast cancer," said U.S. National Cancer Institute Director Andrew C. von Eschenbach, MD, in an NCI news release. "These results are one more example that we are at a major turning point in the use of targeted therapies to eliminate suffering and death from cancer."
While the results of studies such as these reveal that Herceptin can be beneficial for women with advanced breast cancer, Herceptin has also been found to cause serious heart problems (cardiotoxicity). Therefore, all patients who take Herceptin should have their hearts monitored before and during treatment (see Side Effects section below for more information).
In rare cases, women who have been given Herceptin have experienced allergic shock or respiratory distress. These reactions were not observed in clinical trials prior to FDA approval. However, warning labels accompanying Herceptin packaging have since been amended to include these possible effects.
As with all drugs, Herceptin has been shown to cause a variety of side effects, some of which are potentially severe. The common side effects (such as fever, chills, weakness, or nausea) listed in this section occurred in more than 25% of women who were given Herceptin with or without other drugs in clinical studies. These symptoms were treatable and were not as frequent after the initial treatment with Herceptin. The less common side effects listed in this section occurred in less than 10% of women who were given Herceptin with or without other drugs in clinical studies.
Common side effects of Herceptin include:
- Fever
- Chills
- Weakness
- Nausea (especially when given with chemotherapy)
- Diarrhea
- Increased cough
Less common side effects of Herceptin include:
- Heart problems (see explanation below)
- Loss of white blood cells (leukopenia)
- Fatigue or difficulty breathing due to a reduction of red blood cells (anemia)
Heart problems with Herceptin: In a small number of women, Herceptin alone or in combination with chemotherapy can lead to serious heart problems including ventricular dysfunction and congestive heart failure. This life-threatening side effect is more common among patients who receive Herceptin in combination with the AC chemotherapy regimen (chemotherapy consisting of an anthracycline, such as Adriamycin or Ellence, and cyclophosphamide). However, Herceptin is not approved for use with this chemotherapy drug combination outside of the clinical trial setting. However, a study presented at the June 2007 meeting of the American Society of Clinical Oncology reveals that early-stage breast cancer patients who were given Herceptin in combination with chemotherapy did not increase their risk of heart failure when evaluated three to five years later. Women considering Herceptin should have their heart function evaluated by a physician before beginning treatment. Once on Herceptin, women should be closely monitored for any heart problems that may occur.
Tykerb was approved the FDA in 2007 to treat advanced breast cancer in combination with the chemotherapy drug, Xeloda (generic name, capectabine). In January 2010, the FDA expanded the approval of Tykreb for use in advanced breast cancer patients in combination with Femara (generic name, letrozole.
According to GlaxoSmithKline, the drug's maker, Tykerb is a new molecular entity , a kinase inhibitor working through multiple pathways (targets) to deprive tumor cells of signals needed to grow. In its announcement for its approval of Tykerb, FDA described the difference between Tykerb and Herceptin: "Unlike, for example, trastuzumab - a monoclonal antibody, which is a large protein molecule that targets the part of the HER2 protein on the outside of the cell - Tykerb is a small molecule that enters the cell and blocks the function of this and other proteins. Because of this difference in mechanism of action, Tykerb works in some HER2 positive breast cancers that have been treated with trastuzumab and are no longer benefiting." Click here for more information.
Tykerb comes in tablets of 250 milligrams. Typically, an undivided dose of 1,250 milligrams should be taken orally once daily for 21 days and in combination with Xeloda on days 1-14 of a 21 day cycle.
The 1997 FDA-approval of Tykreb, along with Xeloda reflected more than 16 years of research, including more than 60 clinical trials and research studies. In examining data prior to its approval, the FDA reviewed a study that included 400 women with advanced, HER2 positive breast cancer. Half of the women were given Tykerb with Xeloda and the other half were given Xeloda alone. The results of the study showed that the women who received Tykerb with Xeloda had a statistically significant improvement in the time to tumor progression. Specifically, women the length of time it took for the women's cancer to progress was an average of 27.1 weeks on the combination of Tykerb and Xeloda versus 18.6 weeks on Xeloda alone. All of the women had been formerly treated with Herceptin and other cancer treatments. The tumor response rate was also higher among these women.
Furthermore, in research leading to the FDA’s expanded approval of Tykreb, along with Femara, women with HER2-positive disease receiving the Tykerb plus Femara combination more than doubled the time they lived without the cancer progressing compared with those receiving Femara alone (35 weeks vs. 13 weeks). However, according to the FDA, it is too early to determine whether an improvement in overall survival will be observed in the clinical trial. Click here for more information.
As with all drugs, including Herceptin, patients taking Tykerb are at risk of side effects, some of which could be severe. In clinical trials, the severity of side effects with Tykerb was similar to those experienced by patients who were given Herceptin.
Common side effects of Tykerb include:
- Diarrhea
- Nausea
- Vomiting
- Rash
- Hand-foot syndrome which may include numbness, tingling, redness, swelling and discomfort of hands and feet
Some patients also experienced generally reversible heart problems, such as left ventricular ejection fraction, which can cause shortness of breath. The FDA advises patients to talk to their physicians about potential side effects, potential drug interactions, and other medical conditions including heart and liver problems when considering treatment with Tykerb.
- Read about the FDA's expanded use of Tybreb in 2010, http://www.imaginis.com/breast-health/fda-expands-use-of-breast-cancer-drug-tykreb
- Genentech Inc., the manufacturer of Herceptin, maintains a detailed website about Herceptin and HER2. The site is divided into separate sections for patients and health care professionals, http://www.herceptin.com/
- Her-2: The Making of Herceptin, A Revolutionary Treatment for Breast Cancer by Robert Bazell and Amy Bernstein explains how Herceptin was developed. Click here to learn more about this book.
- The March 13, 2007 FDA news release, "FDA Approves Tykerb for Advanced Breast Cancer Patients," was posted on the FDA's website, http://www.fda.gov/
- The March 13, 2007 GlaxoSmithKline news release, FDA approves Tykerb® (lapatinib) in combination with Xeloda (capecitabine) for the treatment of advanced or metastatic breast cancer in women who have progressed on prior therapy," was posted on GlaxoSmithKline's website, http://www.gsk.com/
Update: November 2010
