Femara trial halted due to unprecedented results

A 43% reduction in the risk of breast cancer recurrence and a 46% reduction in disease spreading from one breast to the other have led investigators to halt an international clinical trial and recommend that postmenopausal women who have been treated with tamoxifen for five years are considered for the drug letrozole (Femara, Novartis Oncology).

The results of the study involving nearly 5,200 women and hospitals throughout the world, including the Royal Marsden NHS Trust, were published for early on-line release in the New England Journal of Medicine.

'This is one of the most important advances in the treatment of postmenopausal women with breast cancer, and is a further valuable step in preventing disease recurrence' Professor Ian Smith, The Royal Marsden NHS Trust.

Until now there has been no treatment to address the significant ongoing risk of recurrent breast cancer for women who have completed five years of tamoxifen therapy, as previous studies have shown that women do not benefit from taking tamoxifen for more than five years and are actually exposed to increased risk of endometrial cancer, pulmonary embolism and stroke. Postmenopausal women with early breast cancer, who have taken five years of tamoxifen to stop their cancer from returning, now have the option of extended protective (adjuvant) treatment by going on to take five years of letrozole.

Professor Smith, an investigator and Head of the Breast Unit at the Royal Marsden, continued: 'Letrozole is better than tamoxifen at treating advanced breast cancer and early breast cancer before surgery, so we hoped letrozole would also provide benefits in the extended adjuvant setting after surgery and five years of tamoxifen therapy for early breast cancer. The data surpassed our expectations with letrozole more than doubling the anticipated improvement in disease free survival and nearly halving the risk of breast cancer recurring or spreading to the other breast. We can now offer women who complete five years of tamoxifen therapy another drug which can reduce the risk of their cancer returning even more.'

Based on the strength of the data, Novartis Oncology intend to broaden the current licence for the drug so that in the future women who were not involved in the trial have the opportunity to take Femara after five years of tamoxifen.

The international breast cancer trial of nearly 5,200 women, called MA-17, is the first study ever to examine the effectiveness of an aromatase inhibitor drug, letrozole for five years following five years of treatment with tamoxifen. During this period women are not normally treated despite the ongoing risk of breast cancer recurrence. The results show that after 2.4 years of treatment, women who were taking letrozole experienced a 43% reduction in the risk of recurrence compared to women taking placebo, as well as a 46% reduction in cancer spreading from one breast to the other. After four years of treatment, women taking letrozole experienced an estimated 6% absolute improvement in disease free survival compared with placebo (letrozole 93% vs. 87% placebo). Disease free survival is defined as the time from randomisation to letrozole or placebo to the time of first recurrence of the primary disease in the breast (including the other breast), chest wall, nodal sites or other parts of the body (metastatic disease).

The female hormone oestrogen is involved in the stimulation of some breast cancers. The primary source of oestrogen in postmenopausal women is from fat, liver, muscle, and breast tissue; through a process that turns adrenal androgens into oestrogen. The enzyme known as aromatase converts androgens into oestrogen and it is this oestrogen that stimulates the growth of certain hormone-dependent breast cancer cells. Letrozole binds to the enzyme aromatase and blocks it from converting adrenal androgens to oestrogen reducing the amount of oestrogen circulating around the body.

About Femara

Femara, an oral once-a-day therapy, is currently licensed in the UK for the first-line treatment of hormone receptor positive or hormone receptor unknown locally advanced breast cancer in postmenopausal women and is proven to be superior to tamoxifen as first-line therapy in advanced disease. Femara is also approved for the treatment of advanced breast cancer in postmenopausal women with disease progression following antioestrogen therapy and as neo-adjuvant (preoperative) therapy. Femara is the only drug of its class to hold a licence within the UK to treat breast tumours on a preoperative basis in hormone receptor positive patients.