BIG 1-98: A large multinational initial adjuvant trial comparing an aromatase inhibitor (AI) with tamoxifen.¹

BIG 1-98 is a multicenter, phase 3, randomized, double-blind clinical trial conducted in more than 8000 postmenopausal women with resected hormone receptor positive (HR+) early breast cancer.²

BIG 1-98 was initiated in 1998 and has involved 27 countries worldwide.^2,3

It was coordinated by the International Breast Cancer Study Group (IBCSG)—an independent, international collaborative group of investigators specializing in adjuvant clinical trials.^2-4

The objective of BIG 1-98 was to answer 2 questions^3,4:

1. How does FEMARA^® (letrozole) monotherapy compare with tamoxifen monotherapy?
2. Is sequencing of endocrine therapies superior to monotherapy?

BIG 1-98 study design and patient characteristics

BIG 1-98 study design^2,3,5

^*ITT=Intent-to-treat; excludes 18 patients who withdrew consent and did not receive study treatment.

• Primary end point: Disease-free survival (DFS)^2†
• Secondary end points: Systemic DFS, overall survival, time to recurrence, and time to distant recurrence²

Select patient characteristics at baseline in BIG 1-98 clinical study²

Results from primary core analyses—26-month median follow-up^‡

This analysis 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). In the 2 sequential arms, data were truncated 30 days after switch.^2,3,5

Primary core analysis at 26-month median follow-up^2,3,5

Key question answered: FEMARA^® was shown to be significantly more effective than tamoxifen in reducing overall recurrence, including distant metastases, in postmenopausal patients with HR+ early breast cancer in the initial adjuvant setting.² Click here for detailed efficacy results.

Based on these findings, the protocol was amended in 2005 to offer FEMARA^® to those patients assigned to tamoxifen monotherapy. A total of 619 patients (25.2%) from the tamoxifen monotherapy arms crossed over to receive FEMARA^®.³

Patients crossed over mostly during years 3 to 5 of treatment and received FEMARA^® for a median of 18 months after crossover.³

Results from monotherapy arm analysis (arms A and B only)—73-month
median follow-up

FEMARA^® (letrozole) was compared with tamoxifen in 2 analyses:Intent-to-treat (ITT) and censored^3,6:

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.⁶

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.⁶

Monotherapy analysis at 73-month median follow-up³

Key question answered: At a median follow-up of 73 months and a median treatment duration of 60 months, FEMARA^® was shown to significantly improve DFS and reduce the risk of distant recurrence versus tamoxifen in postmenopausal patients with HR+ early breast cancer in the initial adjuvant setting.³ Click here for detailed efficacy results.

When choosing an initial adjuvant therapy, consider the evidence in BIG 1-98.¹

Now, see detailed efficacy results from the pivotal BIG 1-98 trial, click here.

^†DFS was assessed as the time from randomization to the earliest event of locoregional or distant recurrence (metastases) of the primary
 disease, development of invasive contralateral breast cancer, appearance of a second non-breast primary tumor, or death from any cause
 without a prior cancer event.^5
‡Includes 2-arm and 4-arm options.

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. Fentiman IS. Optimising adjuvant endocrine treatment of breast cancer with aromatase inhibitors. Int J Clin Pract. 2006;60(6):689-693. 2. 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. 3. 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; San Antonio, Texas. 4. Coates AS, Keshaviah A, Thürlimann B, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007;25(5):1-12. 5. FEMARA^® (letrozole) [summary of product characteristics]. Basel, Switzerland: Novartis Pharma AG; 2009. 6. Data on file. Novartis Oncology, East Hanover, NJ.