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Monday 24th October, 2005
NEJM reports that Herceptin® following standard chemotherapy significantly
reduces the risk of disease recurrence.
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
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
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.
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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
Concurrent NCCTG and NSABP studies find trastuzumab best for women
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
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
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
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.
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.