What Have Clinical Trials with Herceptin Shown?

Herceptin was shown to slow the growth and spread of cancerous HER2, Herceptin, and Tykerb | Breast Cancer Treatment | Imaginis - The Women's Health & Wellness Resource Network

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HER2, Herceptin, and Tykerb

What Have Clinical Trials with Herceptin Shown?

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 postive 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.

What are the Side Effects of Herceptin?

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.

What is Tykerb?

Tykerb was approved the FDA in 2007 to treat advanced breast cancer in combination with the chemotherapy drug, Xeloda (generic name, capectabine). 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.

What Have Clinical Trials with Tykerb Shown?

This approval reflects 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. GlaxoSmithKline is continuing to study Tykerb with breast cancer patients as well as those with other types of cancers to see if the drug could be useful for other patients too.

What are the Side Effects of Tykerb?

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.

Additional Resources and References

  • 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: July 2010