ROCKVILLE, MarylandFemara (letrozole tablets, Novartis) has
received marketing approval from the US Food and Drug Administration (FDA) for
the extended adjuvant treatment of postmenopausal women with early breast
cancer who have received 5 years of adjuvant therapy with tamoxifen. The FDA
based its approval on data from the MA-17 trial, an international, independent
study supported by Novartis.
"Femara truly provides hope to women who have survived early
breast cancer by offering them an improved chance of remaining cancer free,"
said Diane Young, MD, vice president and global head of clinical development
for Novartis Oncology. "This priority review approval marks the first time that
nearly 100,000 women in the United States who complete tamoxifen therapy each
year will have a medical option to reduce their ongoing risk of breast cancer
About one-third of estrogen-receptor-positive women treated
for early breast cancer suffer a recurrence of their disease, more than half of
them 5 years or more after their surgery. Although tamoxifen has proved
effective in reducing the risk of the recurrence of breast cancer in such
women, after 5 years, the risks of the drug outweigh its benefits. "Extended
adjuvant treatment with Femara is the first therapy to effectively reduce the
ongoing risk of breast cancer recurrence," Novartis said in a statement
announcing the drug’s new indication. "The term extended adjuvant treatment
describes the period following standard adjuvant treatment with tamoxifen."
Femara is a once-a-day aromatase inhibitor previously
approved by the FDA for the first-line treatment of postmenopausal women with
hormone-receptor-positive or receptor-unknown locally advanced or metastatic
breast cancer, and for treating advanced breast cancer in postmenopausal women
with disease progression following antiestrogen therapy.
The phase III, double-blind, randomized, multicenter MA-17
trial enrolled more than 5,100 postmenopausal women with early breast cancer in
a study coordinated by the National Cancer Institute of Canada’s Clinical
Trials Group at Queens University in Kingston, Ontario. Patients were
randomized to either Femara or placebo.
The trial protocol set disease-free survival as the primary
endpoint, and study data showed that the Femara patients had a 42% reduced risk
of disease recurrence, compared with the placebo group; recurrence included
metastases, contralateral breast cancer, and recurrence within or near the
original site (P = .00003).
The researchers also found that patients in the Femara arm
had a statistically significant 40% lower risk overall of metastases; mortality
was reduced by 39% in women with node-positive breast cancer (P = .035).
With 2.5 years median follow-up, overall survival was
unchanged in node-negative patients, but reductions in local recurrences, new
primary tumors, and distant recurrences were consistent with those seen in
node-positive patients. Among all patients, 18% fewer deaths occurred in the
Femara patients, but at 2.5 years, the difference was not statistically
Interim results from the trial led the MA-17 Independent
Data Safety Monitoring Committee to unblind the study data early in the fall of
2003 and allow researchers to offer the placebo group the opportunity to switch
to Femara. Researchers continue to follow all patients in the trial under an
MA-17 included preplanned substudies to assess Femara’s
effect on bone mineral density and lipid metabolism. Data showed more patients
in the Femara arm than in the placebo set (6.9% vs 5.5%) received a new
diagnosis of osteoporosis (P = .04), but researchers found no
significant difference in clinical fractures between the treatment and placebo
groups (5.9% vs 5.5%). Moreover, there were no significant differences between
the Femara and placebo arms in cardiovascular events or lipid profiles. The HDL-LDL
cholesterol ratio decreased in both groups after 6 months, but the drop was
similar in both groups.
Femara is contraindicated in patients with known
hypersensitivity to the drug or its excipients. Adverse events associated with
Femara are usually mild to moderate. In the MA-17 trial, the most common side
effects in the Femara patients, compared to those on placebo, were hot flashes
(50% vs 43%), arthralgia and arthritis (29% vs 23%), and myalgia (7% vs 5%).