The US regulatory has approved Femara ( Letrozole), a once-a-day oral aromatase inhibitor, in a new indication as a treatment for use after surgery in postmenopausal women with hormone-sensitive early breast cancer,

The US approval was based on results of the BIG 1-98 study, which is published in the The New England Journal of Medicine ( NEJM ).

BIG 1-98 compared the effectiveness and tolerability of Femara versus Tamoxifen ( Nolvadex ) when used as initial therapy after surgery in postmenopausal women with hormone-sensitive early breast cancer.

Femara reduced the risk of breast cancer returning by an additional 21% ( p=0.002 ) over the reduction offered by Tamoxifen.

Further, patients taking Femara showed a 27% ( p=0.0012 ) reduction in the risk of the cancer spreading to distant parts of the body.
Women whose disease does spread to other sites ( metastasis ) may be at greater risk of dying from their disease.

In addition to the overall findings, Femara demonstrated its greatest benefit in two groups of women at increased risk of recurrence.
Femara reduced this risk by 29% in women whose breast cancer had already spread to the lymph nodes at the time of diagnosis and by 30% in women who had undergone chemotherapy.

The data also showed that in these high-risk subgroups, Femara reduced the risk of cancer spreading to distant parts of the body by 33% and 31%, respectively.

Femara is now the only medicine in its class approved by the US Food and Drug Administration ( FDA ) for use as an initial treatment immediately after surgery in patients with this form of breast cancer, as well as following completion of five years of Tamoxifen therapy.
Femara is approved for extended adjuvant treatment of early breast cancer in postmenopausal women who have completed standard adjuvant Tamoxifen therapy.
In addition, it is indicated for first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer and for the treatment of advanced breast cancer in postmenopausal women with disease progression following anti-estrogen therapy, and as neo-adjuvant ( pre-operative ) therapy.

Contraindications, warnings and adverse events

Patients should talk to their doctor if they are allergic to Letrozole or any of its ingredients. Femara should not be taken by women who are pregnant as it may cause fetal harm.
Femara should be taken only by women who are postmenopausal.
Some women have reported fatigue and dizziness with Femara. Patients should use caution before driving or operating heavy machinery until they know how Femara affects them.
In the extended adjuvant setting, longer follow-up is needed to determine the risk of bone fracture associated with long-term use of Femara.

In the adjuvant setting, commonly reported side effects are generally mild to moderate.
Side effects seen in Femara versus Tamoxifen included: hot flashes ( 33.7% vs. 38% ), joint pain ( 21.2% vs. 13.5% ), night sweats ( 14.1% vs. 13.5% ), and weight gain ( 10.7% vs. 12.9% ).
Other side effects seen were bone fractures and osteoporosis.

In the extended adjuvant setting, commonly reported side effects are generally mild to moderate. Those seen more often with Femara versus placebo were hot flashes ( 50% vs 43% ), joint pain ( 22% vs 18% ) and muscle pain ( 7% vs 5% ).
Other side effects, which were comparable to placebo, include fatigue ( 34% vs 32% ), swelling due to fluid retention ( 18% vs 16% ), headache ( 20% vs 20% ), increase in sweating ( 24% vs 22% ) and increase in cholesterol ( 16% vs 16% ).
The percentage of patients on Femara versus placebo reporting a fracture was 5.9% vs 5.5%.
The percentage of patients reporting osteoporosis was 6.9% vs 5.5%.
Bisphosphonates, which are drugs used to increase bone strength, were given to 21.1% of Femara patients and 18.7% of placebo patients.

Source: Novartis, 2005


XagenaMedicine2005