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Monday 24th October, 2005

NEJM reports that Herceptin following standard chemotherapy significantly reduces the risk of disease recurrence.


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Aromasin approved for adjuvant therapy of breast cancer

The HERA adjuvant breast cancer trial recognizes the significance of Herceptin? in early HER2 patients

Brussels, Belgium - The New England Journal of Medicine (NEJM) reports that the administration of Herceptin? (trastuzumab) following standard chemotherapy significantly reduces the risk of disease recurrence for women with early-stage HER2-positive breast cancer by 46%.

The interim results from the international HERA (HERceptin Adjuvant) study provide new hope in the fight against HER2-positive breast cancer, a more aggressive form of the disease affecting approximately 20 ? 30% of women with breast cancer . The HERA study is one of the largest breast cancer trials ever carried out, with more than 5,000 patients in 39 countries. The study allowed the use of a wide range of chemotherapy regimens before treatment with Herceptin, making the results relevant to many parts of the world.

Dr Martine Piccart, lead investigator of the HERA study and Chair of the Breast International Group (BIG), commented, "Breast cancer is a serious and sometimes life-threatening disease, but with appropriate and timely treatment in the early stages, many women can improve their chances of long-term survival. For women with early-stage HER2-positive breast cancer, results from the HERA study provide some much needed optimism. The study showed that Herceptin, a drug designed specifically for HER2-positive breast cancer, can remarkably reduce the risk of cancer returning." Dr. Piccart added, "I can't stress enough how crucial it is that all patients' breast tumours are tested appropriately at initial diagnosis, and if patients are HER2-positive, that they have access to Herceptin."

Results from a joint interim analysis of over 3,000 patients from two North American trials provided similar remarkable results for Herceptin in early-stage HER2-positive breast cancer, and were also published in the NEJM today. These data, at a median follow-up of two years, show that Herceptin in combination with a specific chemotherapy regimen provided a 52% reduction in risk of cancer coming back as well as a 33% reduction in risk of death.

The strength of the results from the HERA study has influenced medical and regulatory organizations around the world to act urgently to ensure access to Herceptin for early-stage HER2-positive breast cancer patients. Several countries are already developing clinical guidelines and committing funding to allow eligible patients faster access, prior to license.

About the HERA study

HERA, conducted by the Breast International Group (BIG) and Roche , is one of the largest adjuvant studies ever carried out among breast cancer patients; enrolment to the trial began in December 2001, and nearly 5,100 HER2-positive patients were enrolled at 480 sites in 39 countries across the world. HERA is a randomized trial, which, following standard adjuvant systemic chemotherapy and radiotherapy (if applicable), evaluates observation versus Herceptin every three weeks for 12 months or 24 months in women with early-stage HER2-positive breast cancer. The HERA study allowed for the use of a wide range of chemotherapy regimens, and both lymph node-positive and lymph node-negative patients were eligible for entry into the trial.

According to the interim analysis, the primary efficacy endpoint was met, showing that in both 12- and 24-month arms, patients who received Herceptin had a statistically significant improvement in disease-free survival (the length of time after treatment during which no disease is found). At a median follow-up of one year, the secondary endpoint of overall survival had not reached statistical significance, but an improvement in overall survival is also possible as the data mature.

The NEJM article provides the results of the comparison between 12 months of Herceptin versus observation, but not a comparison of 12 months versus 24 months treatment duration. The trial will continue to assess this comparison and data are expected in 2008.

All study data are managed by a Brussels-based BIG member group, the Breast European Adjuvant Studies Team (BrEAST), with independent statistical analysis carried out in Boston and Scotland by the non-profit research organization, Frontier Science. The HERA study also has an external Independent Data Monitoring Committee (IDMC) that regularly reviews safety data. No safety concerns were raised by the IDMC, and the incidence of congestive heart failure was very low (0.5% in the Herceptin arm vs. 0% in the observation arm). Patients in this study will continue to be followed for any side effects for up to ten years.

Concurrent NCCTG and NSABP studies find trastuzumab best for women with HER2

JACKSONVILLE, Fla. -- In a joint paper, co-authored by Mayo Clinic's Edith Perez, M.D., and Edward Romond, M.D., of the National Surgical Adjuvant Breast and Bowel Project (NSABP), researchers report complete and combined results of two trials comparing adjuvant chemotherapy with or without concurrent trastuzumab treatment in women with surgically removed HER2-positive breast cancer. The studies showed trastuzumab (Herceptin?) therapy to be highly superior to standard treatment, reducing recurrence of cancer by half. The findings will be published in the Oct. 20, 2005, issue of The New England Journal of Medicine.

"Herceptin has changed the treatment of breast cancer," says Dr. Perez, who is the co-director of Mayo Clinic's Multidisciplinary Breast Clinic in Jacksonville, Fla. "When we started this study, I knew in my heart results would be positive, but this by far exceeded my expectations."

Of the 2,043 patients enrolled in NSABP trial B-31 and 1,633 patients enrolled in the two reported treatment groups of the North Central Cancer Treatment Group (NCCTG ) trial N9831 by the end of 2004, complete follow-up information was available on 3,351 patients. Two hundred sixty-one women in the control group (1,679 patients) had a recurrence of breast or other primary cancer as compared to 133 in the group receiving trastuzumab. At three years, 90.4 percent of women receiving trastuzumab were disease free, compared to 81.5 percent of women in the control group. There also was a measurable reduction in the development of other non-breast primary cancers in the B-31 trial for women receiving trastuzumab. Overall survival also appeared to be impacted, with only 62 deaths in the trastuzumab group as compared with 92 in the control group.

Dr. Perez and her co-investigators found convincing evidence that women with HER2-positive breast cancer can now be treated more effectively. "A million women each year are diagnosed with breast cancer throughout the world, and approximately 25 percent of them have HER2 tumors," said Dr. Perez. "To be able to find a treatment that impacts the lives of so many is a huge success for the cancer research community."

The NCCTG trial N9831, of which Dr. Perez was the primary investigator, was a cooperative effort with the Eastern Cooperative Oncology Group (ECOG), the Southwest Oncology Group (SWOG), and the Cancer and Leukemia Group B (CALGB). It compared three chemotherapy regimens, two that included trastuzumab therapy -- one dosage concurrent with weekly paclitaxel, the other after completion of paclitaxel. The NSABP trial B-31 compared one chemotherapy regimen against the same regimen with weekly trastuzumab and tri-weekly (or weekly) paclitaxel. Investigators determined that the treatments being compared were similar, and results from the two studies were combined to form a joint analysis, excluding the NCCTG N9831 trial group that looked at trastuzumab administered sequentially after paclitaxel.


Editor's Notes

About breast cancer and Herceptin
Eight to nine percent of women will develop breast cancer during their lifetime, making it one of the most common types of cancer in women. Each year more than one million new cases of breast cancer are diagnosed worldwide, with a death rate of nearly 400,000 people per year.

In HER2-positive breast cancer, increased quantities of the HER2 protein are present on the surface of the tumour cells. This is known as 'HER2 positivity.' High levels of HER2 are present in a particularly aggressive form of the disease. Research shows that HER2-positivity affects approximately 20-30% of women with breast cancer.

Herceptin is a humanised antibody, designed to target and block the function of HER2, a protein produced by a specific gene with cancer-causing potential. Herceptin has demonstrated improved survival in the advanced (metastatic) setting, where its addition to chemotherapy allows patients to live up to one-third longer than chemotherapy alone. Herceptin received approval in the European Union in 2000 for use in patients with metastatic breast cancer, whose tumours overexpress the HER2 protein, as first-line therapy in combination with paclitaxel where anthracyclines are unsuitable, and as a single agent in third-line therapy. In 2004, it also received approval for use in combination with docetaxel as a first-line therapy in HER2-positive patients who have not received chemotherapy for their metastatic disease. Herceptin is marketed in the United States by Genentech, in Japan by Chugai and internationally by Roche. Since 1998, Herceptin has been used to treat over 230,000 HER2-positive breast cancer patients worldwide.


1.Piccart-Gebhart M, Procter M, Leyland-Jones B, et al. A Randomized Trial of Trastuzumab Following Adjuvant Chemotherapy in Women with HER2 Positive Breast cancer. New England Journal of Medicine 353:16 2005.
2.Harries M, Smith I. The development and clinical use of trastuzumab (Herceptin). Endocr Relat Cancer 9: 75-85, 2002.
3. Romond, E., Perez, E. et al. Trastuzumab plus Adjuvant Chemotherapy for Operable HER2 Positive Breast Cancer. New England Journal of Medicine 353:16 2005.
4.World Health Organization, Globocan 2000: Cancer Incidence, Mortality and Prevalence Worldwide. 2000.
5. Mayo Clinic.

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