Herceptin: Positive Results Tempered by Concern About Side Effects
February 7, 2006
Herceptin: 'Simply Stunning' Results Tempered by Concern About Side-Effects
In test results researchers describe as "simply stunning", Herceptin (trastuzumab)-a drug already used in treatment of advanced cancer-has been shown to halve the recurrence of breast tumors after standard therapy.
However, Herceptin works only in women whose breast tumors contain high amounts HER2, a protein that makes the cancer particularly aggressive; moreover, the drug can cause significant effects, according to a report by Reuters on 20 October.
About 20% of women with breast cancer have this type of tumor, so about 42,000 women in the Untied States could benefit from Herceptin treatment, according to Reuters. About 400,000 people worldwide die from breast cancer each year.
Results of two studies on Herceptin were published in the New
England Journal of Medicine (NEJM) on 20 October 2005.
Study 1
Study
2
Trastuzumab is sold under brand-name Herceptin by Genentech Inc. in the US and by Swiss drug manufacturer Roche in Europe.
"This is a very important finding. It's likely to change the recommended care for patients. But we need to know more about the side effects and the long-term effectiveness," said Richard Gelber of the Dana-Farber Cancer Institute and an author of one study (the "HERA" study), according to Reuters.
"The results are simply stunning," said Gabriel Hortobagyi of the University of Texas MD Anderson Cancer Center in Houston, according to Reuters. Hortobagyi predicted in a NEJM editorial that the findings "will completely alter our approach to the treatment of breast cancer."
Last May, when preliminary findings were first released at the American Society of Clinical Oncology annual conference, the presenters received a standing ovation, according to Reuters.
Clinical Trials of Herceptin
Researchers conducted three international clinical trials that included over 6,500 patients. Results showed that Herceptin, which has previously primarily been used to enhance survival of patients with advanced HER2 breast cancer, is also highly effective in treating patients in the early stages of breast cancer also, according to a report in TurkishPress.com.
A NEJM summary of the trials described the results as being so impressive that Herceptin could lead to "a cure" for breast cancer.
"This is probably the biggest evidence of a treatment effect I've ever seen in oncology", said Gelber, according to TurkishPress.com. "It is quite remarkable."
Herceptin and HER2
HER2 is a particularly aggressive protein that is involved in up to 30% of the more than one million new breast-cancer cases diagnosed worldwide each year. HER2 is often resistant to chemotherapy.
Herceptin is a monoclonal antibody drug (generic name trastuzumab) that has been used since 1998 to treat women in the advanced stages of HER2-positive breast cancer following chemotherapy. Herceptin blocks HER2 activity to prevent the cancer's recurrence.
In the largest clinical trial to date, in 2001 the Breast International Group teamed up with Roche (Herceptin's European manufacturer) to test the drug's effect on 5,000 women in 39 countries who had been were diagnosed with early-stage HER2-positive breast cancer.
Within one year, women who received Herceptin showed unusually high positive results-the recurrence rate of breast cancer was reduced 46%. Consequently, two years after treatment began, 8% more women were free of breast cancer.
Concerns About Side Effects - Cardiotoxicity
As with many new drugs, the good news about Herceptin is tempered by concerns about side effects.
Studies show that trastuzumab may cause heart damage in some women, although these problems usually fade if treatment is discontinued, Gelber reportedly told Reuters. Moreover, women who receive Herceptin after breast-cancer surgery have a higher risk of developing subsequent tumors in the brain or elsewhere in the nervous system.
Another study showed that herceptin, when combined with anthracycline-based chemotherapy, offers optimal disease-free survival for women with breast cancer. However, this study also showed that the benefits come at a cost of increased cardiotoxicity.
Results of the trial were presented at the San Antonio Breast Cancer Symposium 2005 and reported by MedPage Today on December 8, 2005.
Dennis Slamon, MD, PhD, director of the Jonsson Comprehensive Cancer Center at UCLA, and colleagues conducting The Breast Cancer International Research Group 006 trial randomized 3,222 women to one of three regimens:
- A control arm of Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxotere (docetaxel)-also called "AC-T";
- An investigational arm with the same regimen, but with Herceptin delivered at the same time as the Taxotere-"AC-TH";
- An additional investigational arm consisting of Taxotere, Paraplatin (carboplatin) and Herceptin, administered concurrently-"TCH".
Both of the Herceptin-containing regimens increased disease-free survival between 39% (TCH) and 51% (AC-TH), compared with the control arm (AC-T), Dr Slamon reported at the San Antonio Breast Cancer Symposium.
However, interim analysis of trial data from about 2,100 participating women confirmed that Herceptin and anthracycline drugs, such as Adriamycin, interact to cause cardiotoxicity.
"The mantra has been that this is not a problem because these patients get better," Dr Slamon reportedly said. "But this phenomenon is real and it is not short-term."
Overall, the study showed that the efficacy of the TCH regimen is nearly as high as that so the AC-TH regimen, but with considerably less cardiotoxicity. The TCH regimen is therefore a more suitable potential treatment for patients with a higher risk for cardiac complications, Dr Slamon reportedly said.
For more on Herceptin, visit these websites:
- National Cancer Institute
- BreastCancer.org
- ClinicalTrials.gov (for information on the Herceptin clinical trial)
Sources:
Breast
cancer drug Herceptin results 'simply stunning': scientists,
TurkishPress.com, 20 October 2005.
Drug halves breast cancer relapse rate for some, Reuters, 20
October 2005.
Trastuzumab
after Adjuvant Chemotherapy in HER2-Positive Breast Cancer,
Martine J. Piccart-Gebhart, MD, PhD, et al., The New England
Journal of Medicine, volume 353, pages 1659-1672, 20 October
2005.
Trastuzumab
plus Adjuvant Chemotherapy for Operable HER2-Positive Breast
Cancer, Edward H. Romond, MD, et al., The New England
Journal of Medicine, volume 353, pages 1673-1684, 20 October
2005.
The
Distinctive Nature of HER2-Positive Breast Cancers, Harold J.
Burstein, MD, PhD, The New England Journal of Medicine,
volume 353, pages 1652-1654, 20 October 2005.
SABCS:
Herceptin-Anthracycline Cardiotoxicity Called Real and
Persistent, MedPage Today, 8 December 2005.
San Antonio Breast Cancer Symposium
2005
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