FEMARA^® significantly improves disease-free survival (DFS) as initial adjuvant therapy for postmenopausal women with hormone receptor positive (HR+) in early breast cancer.¹

At 26-month median follow-up, FEMARA^® delivered a significant 19% reduction in overall risk of recurrence in BIG 1-98^1,2-a large multinational initial adjuvant trial comparing an aromatase inhibitor (AI) with tamoxifen³

Significant reduction in overall risk of recurrence
at 26-month median follow-up in BIG 1-98 study^1,2

BIG 1-98: a phase 3, randomized, double-blind trial of FEMARA^® versus tamoxifen as initial adjuvant therapy for early breast cancer¹

• The primary core analysis at 26-month median follow-up includes data from 4922 patients randomized to monotherapy (arms A and B) and truncated data at 2 years from 3088 patients randomized to sequential adjuvant therapy (arms C and D)^1-3
• In the 2 sequential arms, data were truncated 30 days after switch^1,3

References: 1. The Breast International Group (BIG) 1-98 Collaborative Group. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005;353(26):2747-2757. 2. Mouridsen H, for the BIG 1-98 Collaborative Group. Letrozole monotherapy vs. tamoxifen monotherapy or vs. letrozole in sequence with tamoxifen for postmenopausal women with endocrine-responsive early breast cancer. Presented at: 31st Annual San Antonio Breast Cancer Symposium (SABCS); December 10-14, 2008; San Antonio, Texas. 3. FEMARA^® (letrozole) [summary of product characteristics]. Basel, Switzerland: Novartis Pharma AG; 2009.

But FEMARA^® also helps protect your patients from the most serious threat¹* …

Breast cancer recurrence initially peaks 2 years after surgery and is mainly due to distant metastases, which are associated with the lowest survival rates compared with other recurrences.^4,5†

FEMARA^® (letrozole) can help you protect significantly more patients from distant metastases early on¹

FEMARA^® is the only AI versus tamoxifen that significantly reduces the early risk of distant metastases^1,2,6*

At 26-month follow-up in BIG 1-98, FEMARA^® delivered:

• Significant 27% reduction in the risk of distant metastases versus tamoxifen^1,2

Significant reduction in risk of distant metastases
at median 26-month follow-up in BIG 1-98 study¹

• Nonsignificant 14% reduction in risk of mortality versus tamoxifen (P=0.15)¹

Standard adjuvant treatment duration is 5 years or until relapse¹ …

Over time, FEMARA^® (letrozole) continues to provide protection against distant metastases⁷

At 73-month median follow-up in BIG 1-98, FEMARA^® is the only AI treatment versus tamoxifen to both^7,8:

• Significantly improve disease-free survival⁷ and
• Significantly improve time to distant recurrence⁷

At a median follow-up of 73 months and a median treatment duration of 60 months, the risk of a disease-free survival event was significantly reduced with FEMARA^® compared with tamoxifen (intent-to-treat [ITT] analysis: HR 0.87; 95% CI: 0.76-0.99; P=0.03; censored analysis: HR 0.84; 95% CI: 0.73-0.95), confirming the 2005 PCA results.⁹

Similarly, the updated analysis confirmed the superiority of FEMARA^® in reducing the risk of distant metastases (HR 0.85; 95% CI: 0.72-1.00). Additionally, while not statistically significant, overall survival trended toward significance in the ITT analysis.⁹

Explanation of ITT versus censored analyses

ITT analyses were conducted ignoring the selective crossover. Censored analyses were conducted censoring follow-up/event times at the date of selective crossover in 632 women (26%) who crossed to FEMARA^® or another aromatase inhibitor after the tamoxifen arms were unblinded in 2005, based on superior efficacy of FEMARA^® over tamoxifen and following the recommendations of the Data Monitoring Committee.⁹

Of these 632 women, 448 (70%) crossed to FEMARA^® to complete initial adjuvant therapy. All of these women were in Option 1 and most crossed in Years 3 to 4, at a median 43 months from randomization. Median duration of FEMARA^® after crossing was 17 months. The remaining 184 women crossed to FEMARA^® (172 women) or another aromatase inhibitor (12 women) to start extended adjuvant treatment, having received tamoxifen for 4.5 to 5 years.⁹

BIG 1-98 monotherapy update at
median 73-month median follow-up⁷

^‡FEMARA^®:tamoxifen—breast cancer events, 321:363; second (nonbreast) malignancy, 101:115; deaths without prior cancer event, 87:87.

At 73-month median monotherapy follow-up,* FEMARA^® was compared with tamoxifen in 2 analyses¹:

• Intent-to-treat (ITT),^† in which the tamoxifen arm included 26% of patients who crossed over to FEMARA^® in years 3 to 5^1,2‡
• Censored,^§ in which patients who crossed over to FEMARA^® were excluded at the time of switch^1,2

^*All protocol-specified treatment finished.^1
†Includes all patients and all events.^2
‡Based on significant benefits seen with FEMARA^® in the primary core analysis, the protocol was amended in
 2005 to offer FEMARA^® to those patients assigned to tamoxifen monotherapy. A total of 632 patients (26%)
 from the tamoxifen monotherapy arm crossed over to receive FEMARA^®.^1
§Includes all patients, but excludes the follow-up events of tamoxifen patients who crossed over to FEMARA^®
 from the time they switched.²

References: 1. Mouridsen H, for the BIG 1-98 Collaborative Group. Letrozole monotherapy vs. tamoxifen monotherapy or vs. letrozole in sequence with tamoxifen for postmenopausal women with endocrine-responsive early breast cancer. Presented at: 31st Annual San Antonio Breast Cancer Symposium (SABCS); December 10-14, 2008; San Antonio, Texas. 2. Data on file. Novartis Oncology, East Hanover, NJ.

So, for your postmenopausal patients with HR+ early breast cancer, consider the threat …

• Distant metastases, which initially peak 2 years after surgery, are associated with the lowest survival rates compared with other recurrences^4,5

...and start and stay with FEMARA^® (letrozole) to help prevent distant metastases^1,2,7

• FEMARA^® is the only AI versus tamoxifen that provides protection from distant metastases during both this early peak of risk and beyond^1,6,7

The unique efficacy profile of FEMARA^® in the initial adjuvant setting is accompanied by a demonstrated safety profile, click here.

^*Distant disease-free survival is a secondary end point of BIG 1-98; the primary end point of the study is disease-free
 survival. Approval is based on a median 26-month follow-up.^1
†In postmenopausal patients with HR+ early breast cancer.^4,5

FEMARA^® is indicated for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer.

Click here for Important Safety Information for FEMARA^®.

References: 1. FEMARA^® (letrozole) [summary of product characteristics]. Basel, Switzerland: Novartis Pharma AG; 2009. 2. The Breast International Group (BIG) 1-98 collaborative. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005;353(26):2747-2757. 3. Fentiman IS. Optimising adjuvant endocrine treatment of breast cancer with aromatase inhibitors. Int J Clin Pract. 2006;60(6):689-693. 4. Mansell J, Monypenny IJ, Skene AI, et al. Distant metastasis—the most common type of early recurrence with adjuvant tamoxifen therapy. Poster presented at: 30th Annual San Antonio Breast Cancer Symposium; December 13-16, 2007; San Antonio, TX. 5. Rugo H, Rourke M, Dranitsaris G, Kaura S. Letrozole or anastrozole for the prevention of early recurrences in post menopausal women with early stage breast cancer: using number needed to treat (NNT) to compare benefit (abstract). EJC Supplements. 2008;6(7):118 (Abstract 236). 6. Gradishar W. Landmark trials in endocrine adjuvant therapy for breast carcinoma. Cancer. 2006;106(5):975-981. 7. Mouridsen H, for the BIG 1-98 Collaborative Group. Letrozole monotherapy vs. tamoxifen monotherapy or vs. letrozole in sequence with tamoxifen for postmenopausal women with endocrine-responsive early breast cancer. Presented at: 31st Annual San Antonio Breast Cancer Symposium (SABCS); December 10-14, 2008; San Antonio, Texas. 8. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008;9:45-53. 9. Data on file. Novartis Oncology, East Hanover, NJ.