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Study's final report confirms letrozole's
benefit for breast cancer patients
Aromatase inhibitor improves survival
for some patients, reduces metastasis
BOSTON - September 6, 2005 - The complete analysis of data
from an international trial of the drug letrozole (Femara) confirms
earlier reports that the drug reduced the recurrence of breast cancer
in women previously treated with tamoxifen. It also finds that letrozole
prevents the development of metastases, even in women whose cancer
had originally spread to their lymph nodes. The report appears in
the September 7 issue of the Journal of the National Cancer Institute.
"The most important new findings we describe in this article
are that letrozole treatment can improve the survival of women with
node-positive disease and can reduce the chance that metastatic
tumors will develop," says Paul E. Goss, MD, PhD, who led the
investigation. At the study's outset, Goss was with the Princess
Margaret Hospital in Toronto; he now is director of Breast Cancer
Research at Massachusetts
General Hospital Cancer Center.
Letrozole is one of a class of drugs called aromatase inhibitors
that suppress the production of estrogen. Estogen stimulates the
growth of breast tumors that express the estrogen receptor, and
drugs that block the production or the action of the hormone are
used in the treatment of those tumors. The most widely used estrogen-blocking
drug is tamoxifen, which becomes ineffective after five years of
treatment, probably because tumor cells become resistant to or even
dependent on the drug.
The international study, called the MA.17 trial, was conducted through
the National
Cancer Institute of Canada and designed to test whether letrozole
could reduce tumor recurrence and increase survival in postmenopausal
breast cancer patients who had completed five years of tamoxifen
treatment. More than 5,000 women were enrolled and randomly assigned
to receive either letrozole or a placebo for an additional five
years. The study was halted in October 2003 - four years after it
began - when an interim data analysis showed that the tumors of
women taking letrozole were significantly less likely recur. Those
results were published in the November 6, 2003 New England Journal
of Medicine.
The current report analyzes all the data compiled during the MA.17
trial and confirms that the risk of recurrence was almost 5 percent
lower in those receiving letrozole than in the placebo group. Women
receiving the drug also had a 39 percent reduction in the risk of
metastasis. While overall survival differences between the two groups
were not significant, among women whose tumors had spread to their
lymph nodes and those who had received tamoxifen for more than five
years, letrozole was associated with significantly better overall
survival.
Although participants taking letrozole did have a greater incidence
of osteoporosis, there was no significant difference in reported
fractures. There was also no increased risk of cardiovascular problems,
which Goss says is particularly noteable. "A recent trial comparing
letrozole to tamoxifen found that letrozole might be associated
with heart problems. But our study, the only placebo-controlled
trial of an aromatase inhibitor, found no such association. A possible
explanation of the earlier study was that tamoxifen may actually
protect against cardiovascular disease, which our results support."
Goss adds that current and future studies will investigate two key
questions about letrozole and other aromatase inhibitors - how long
treatment should continue and whether the drugs also can benefit
women who previously stopped taking tamoxifen or never took that
drug. One trial that has already begun will continue following the
women who received letrozole throughout the MA.17 trial and re-randomize
them to receive either letrozole or a placebo for an additional
five years. Another study will examine tumor samples from all MA.17
trial participants to search for molecular fingerprints that might
identify who would most benefit from letrozole treatment.
Along with Goss, who is a professor of Medicine at Harvard Medical
School, the co-authors of the JNCI study are James Ingle, MD, Mayo
Clinic; Silvana Martino, DO, John Wayne Cancer Institute; Nicholas
Robert, MD, Inova Fairfax Hospital, Falls Church, Virginia; Hyman
Muss, MD, University of Vermont; Martine Piccart, MD, Institut Jules
Bordet, Brussels; Monica Castiglione, MD, University of Bern; Dongsheng
Tu, PhD, Lois Shepherd, MD, Michael Palmer, MSc, and Joseph Pater,
MD, National Cancer Institute of Canada Clinical Trials Group; Kathleen
Pritchard, MD, Toronto-Sunnybrook Regional Cancer Centre; Robert
Livingston, MD, University of Washington; Nancy Davidson, MD, Johns
Hopkins Hospital; Larry Norton, MD, Memorial Sloan-Kettering Cancer
Center; Edith Perez, MD, Mayo Clinic, Florida; Jeffrey Abrams, MD,
National Cancer Institute; and David Cameron, MD, Western General
Hospital, Edinburgh. The study was supported by the Canadian Cancer
Society, the National Cancer Institute of Canada, the U.S. National
Cancer Institute, and Novartis Pharmaceuticals, which markets letrozole
under the brand name Femara.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $450 million
and major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham
and Women's Hospital joined to form Partners HealthCare System,
an integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
Media Contact: Emily
Parker, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
Information about Clinical Trials
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