Postmenopausal women with early breast cancer who completed five years of post-surgical hormonal therapy with tamoxifen benefited significantly from extended adjuvant treatment with Femara (letrozole), according to interim results of a study published for early online release in New England Journal of Medicine. The data prompted an Independent Data Monitoring Committee to unblind the study so that patients in the control arm could consider switching from placebo to Femara, according to an announcement at a press conference held today in Toronto, Canada. This international study was coordinated by the National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario.

"Historically, there has been no proven post-tamoxifen therapy to address the significant ongoing risk of recurrent breast cancer," said Paul Goss, MD, director of Breast Cancer Prevention and Research, Princess Margaret Hospital, Toronto, Canada. "The data announced today provide the first clinical evidence that extended adjuvant drug therapy with Femara, following five years of treatment with tamoxifen, may have a substantial impact on the overall treatment outcome for postmenopausal breast cancer patients." Dr. Goss conceived of, and was international chair of, the clinical trial.

The international breast cancer trial of nearly 5 200 women, called MA-17, is the first study to examine the effectiveness of an aromatase inhibitor, Femara, in the extended adjuvant setting, the period following five years post-surgery tamoxifen treatment. During this period, women do not typically receive drug therapy, despite the ongoing risk of breast cancer recurrence.

At a median follow-up of 2.4 years, the data in the Femara group showed a 43 per cent reduction in risk of overall recurrence compared with placebo (P=0.00008) as well as a significant reduction (46 per cent) in spreading contralateral disease, cancer occurring in the other breast. The estimated absolute improvement in disease-free survival at four years was 6 per cent for postmenopausal patients taking Femara compared with placebo (93 per cent Femara vs. 87 per cent placebo). Disease-free survival is defined as the time from randomization to the time of first recurrence of the primary disease in the breast (including contralateral breast), chest wall, nodal or metastatic sites.

According to data from the Early Breast Cancer Trialists' Group, Oxford, UK, more than 50 per cent of breast cancer recurrence happens in women later than five years after initial diagnosis. Tamoxifen, which reduces the risk of breast cancer recurrence during the first five years of post-surgical therapy, has been shown not to be beneficial beyond five years of treatment. Approximately one million postmenopausal women worldwide currently receive tamoxifen therapy for reduction of breast cancer recurrence. Tamoxifen is currently considered the gold standard hormonal therapy during the first five years of treatment in this population.

"With this trial, significant progress is being made towards addressing a critical challenge faced by post-menopausal women who have completed early adjuvant treatment for breast cancer - the need to protect against the ongoing risk of recurrence following tamoxifen therapy," said Diane Young, MD, vice president, global head, Clinical Development, Novartis Oncology. "Femara has continuously demonstrated remarkable results, and we look forward to data from our ongoing clinical program."

Femara, an aromatase inhibitor, is an oral once-a-day first-line treatment for postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer. It is also approved for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy, and as neoadjuvant (pre-operative) therapy. Femara is currently available in more than 75 countries worldwide. Not all indications are available in every country.

In the MA-17 analysis, the most common adverse events were hot flashes, sweating, edema, hypercholesterolemia, headache, arthralgia, myalgia, fatigue, constipation and dizziness, in greater than 10 per cent of patients in either arm of the study. Of these, hot flashes, arthralgia, and myalgia were more common in those receiving Femara than placebo (P<0.05). Vaginal bleeding was more common in those taking placebo (P<0.05).

The number of women reporting a new bone fracture to date is 77/2166 (3.6%) in the Femara group, compared with 63/2157 (2.9%) in the placebo group (P=0.24). The authors noted a trend to more newly diagnosed osteoporosis in women taking Femara (124/2166 [5.7%]) vs. placebo (97/2157 [4.5%]) (P=0.07).

Femara is contraindicated in patients with known hypersensitivity to Femara or any of its excipients. Femara is generally well tolerated. In a first-line registration trial versus the antiestrogen tamoxifen, the most commonly reported adverse events for Femara were bone pain (22% vs. 21%), hot flushes (19% vs. 16%), back pain (18% vs. 19%), nausea (17% vs. 17%), dyspnea or labored breathing (18% vs. 17%), arthralgia (16% vs. 15%), fatigue (13% vs. 13%), coughing (13% vs. 13%), constipation (10% vs. 11%), chest pain (6% vs. 6%) and headache (8% vs. 6%). Femara may cause fetal harm when administered to pregnant women. There is no clinical experience to date on the use of Femara in combination with other anticancer agents. The incidence of peripheral thromboembolic events, cardiovascular events, and cerebrovascular events was 3-4% in each treatment arm.

In India breast cancer is prevalent in around 160,000 women with 60,000 new cases detechted each year. Treatment options include surgery, radiotherapy, hormonal therapy and chemotherapy.