New early breast cancer treatment significantly reduces the risk of cancer returning

www.astrazeneca.caJul 15 2004

Marking the first major treatment advance since tamoxifen's introduction over 25 years ago, Canada's leading oncologists and breast cancer patient support and advocacy groups gathered to applaud a new era in treatment for early breast cancer.

Women have the best chance of cure at this stage of disease. The recent approval of ARIMIDEX(R) (anastrozole) by Health Canada for post-menopausal patients with hormone- sensitive early breast cancer (EBC), provides the first hormonal alternative to tamoxifen, which had been considered the gold standard for early breast cancer, until now.

"Unlike promising research announcements, this has immediate implications for post-menopausal women with early breast cancer. As of this minute, women can talk to their doctors about taking ARIMIDEX, the only medication approved and proven to have advantages over tamoxifen in terms of disease recurrence in this setting," says Dr. John Mackey, medical oncologist at the Cross Cancer Institute in Edmonton, Alberta.

"Research has shown that the first 2-1/2 years post-surgery are the most critical in terms of recurrence for women diagnosed with early breast cancer," Dr. Mackey continued, "The data we have demonstrate that ARIMIDEX reduces disease recurrence during this important period better than tamoxifen."

Dr. Shail Verma, medical oncologist at the Ottawa Hospital General Campus, notes, "Tamoxifen is an effective medication, and when it was first introduced in Canada 25 years ago, we saw significant gains in survival for breast cancer patients. ARIMIDEX's approval for use in early breast cancer represents an advancement of a similar magnitude. Women with breast cancer have every reason to be optimistic about their outcomes. ARIMIDEX offers safety advantages over tamoxifen which are important to women especially those who have potentially been cured of their breast cancer following surgery".

Dr. Verma continued, "The ATAC trial has shown ARIMIDEX to be significantly more effective than tamoxifen. ARIMIDEX reduced the risk of breast cancer returning by 18 per cent for women with hormone sensitive tumours, and the risk of developing a new breast cancer in the opposite breast by a significant 44 per cent. Tamoxifen is already known to reduce the appearance of new breast cancers by 47 per cent, and the ARIMIDEX benefit was in addition to this".

"The goal for doctors treating cancer is to offer the optimal treatment first to reduce the chances of recurrence, using drugs that are both safe and effective," comments Dr. Kathleen Pritchard, medical oncologist at Sunnybrook and Women's College Health Sciences Centre. "The four year ATAC trial data demonstrates that ARIMIDEX provides the safety, tolerability and efficacy women are looking for in preventing their breast cancer from returning."

"Another breast cancer announcement? We say thank goodness for that," says Jackie Manthorne, executive director, Canadian Breast Cancer Network. "While a cure for breast cancer is now on the horizon, investments in research, innovations and discoveries, along with the growing number of patients participating in clinical trials is paving the way."

Dallas Petroff, executive director, Willow Breast Cancer Support & Resource Services comments, "A new era in treatment is dawning, with better, safer options available. On behalf of everyone touched by breast cancer, we applaud this advance."

While both ARIMIDEX and tamoxifen are hormonal therapies, they work differently to block the action of estrogen. ARIMIDEX blocks the aromatase enzyme and reduces the levels of circulating estrogens in the body and in the cancer itself. Because ARIMIDEX's method of action differs from tamoxifen, it has also demonstrated important side effect benefits versus tamoxifen. Women receiving ARIMIDEX in the ATAC trial(ii) experienced significantly reduced hot flushes, vaginal bleeding, endometrial cancer, strokes and venous thromboembolic events (blood clots). Women taking ARIMIDEX in the ATAC trial did experience more fractures and joint disorders than those receiving tamoxifen, which is known to have a positive effect on bone mineral density. However, fracture rates stabilized over time.

"When I heard I had breast cancer, I was stunned. I'm so thankful that I was given the opportunity to take ARIMIDEX," said breast cancer patient Joan Bain, Vancouver, British Columbia. "Today's news is encouraging for post- menopausal women with breast cancer because it gives us peace of mind that our treatment will reduce our chances of recurrences and, hopefully, let us lead a better, longer life."

• Health Canada's Therapeutic Product Directorate (TPD) granted the conditional approval of ARIMIDEX for post-menopausal patients with hormone receptor positive early breast cancer (EBC). TPD grants a notice of compliance with conditions (NOC/c) to ensure early market access to promising new drugs for diseases that are serious or life threatening, where the new drug appears to provide benefit over available therapy, or where no therapy currently exists. This approval is conditional under further confirmation of clinical benefit. Patients should be advised of the conditional nature of the authorization.
• ARIMIDEX is a highly selective, non-steroidal oral aromatase inhibitor used in the hormonal (endocrine) treatment of breast cancer in post-menopausal women.
• ARIMIDEX is a hormonal treatment for breast cancer known as an aromatase inhibitor. ARIMIDEX is the only new treatment to be approved by Health Canada for use in early breast cancer (EBC) in 25 years.
• Based on the ATAC trial results, ARIMIDEX has been approved as an adjuvant treatment for post-menopausal women with hormone-sensitive, early breast cancer in over 60 countries, including the USA, UK, Japan, Australia, Switzerland, Germany, Spain, and now Canada.
• Until now, ARIMIDEX has been approved for use only in patients with advanced stage breast cancer. Based on the findings of the largest international breast cancer study ever conducted (the ATAC trial - Arimidex, Tamoxifen, Alone or in Combination), this new indication provides an important new option for women with EBC.
• Tamoxifen is an anti-estrogen and acts primarily to prevent estrogen binding to its receptor at tumour sites. Tamoxifen has some partial estrogenic activity, which may be responsible for the differences in its side-effect profile compared with ARIMIDEX.
• ARIMIDEX is an aromatase inhibitor and acts differently to tamoxifen in that it blocks the production of estrogen by the aromatase enzyme pathway - the primary source of estrogen in post-menopausal women, whose ovaries no longer function.
• In the ATAC Trial, ARIMIDEX was found to be superior to tamoxifen in the treatment of post-menopausal women with early breast cancer. Study results at a median of 47 months follow-up suggest an 18 per cent reduction in risk among hormone-sensitive, early breast cancer patients; (HR(*)=0.82 (CI(*): 0.70 - 0.96), p=0.014).(iv)
• The absolute difference between the two treatments continues to increase as shown by continued divergence of the Kaplan-Meier curves; disease free survival (DFS) estimates at four years were 86.9 per cent versus 84.5 per cent for ARIMIDEX and tamoxifen respectively. Therefore, the absolute difference in DFS rates has increased from 2.0 per cent at three years (at the time of the major analysis) to 2.4 per cent at four years. In the clinically relevant hormone- sensitive population, this absolute difference is even greater at 2.9 per cent (89.0 per cent versus 86.1 per cent). At the time of this updated analysis, 46 per cent of patients have completed more than four years' follow-up.(v)
• ARIMIDEX was first marketed in Canada in 1996 and, in addition to the new adjuvant indication, is licensed for use in the first and second- line treatment of advanced breast cancer in post-menopausal women.