New long-term data from a major international breast cancer study reports that postmenopausal woman with hormone receptor-positive early-stage breast cancer who took Femara (letrozole) for five years following surgery had a 13 per cent (P=0.08) reduced risk of death, when compared with tamoxifen.

These results are from a protocol-defined Intent-to-Treat (ITT) analysis (median follow-up of 76 months) of the Femara and tamoxifen monotherapy arms in the Breast International Group (BIG) 1-98 study. The suggested survival benefit from the ITT analysis is important considering that approximately 25 per cent of patients in the tamoxifen arm selectively crossed over to Femara therapy after the tamoxifen arm was unblinded in 2005. While not statistically significant, these are the first data to suggest a survival benefit for an aromatase inhibitor versus tamoxifen in the monotherapy setting immediately following surgery.

To explore the impact of the selective crossover, an additional analysis was conducted censoring follow-up times at the date of crossover to letrozole. In this analysis, a 19 per cent reduction in risk of death (HR=0.81, 95% CI: 0.69-0.94) was observed in favour of Femara.

The International Breast Cancer Study Group (IBCSG) presented these results from the BIG 1-98 trial today at the 31st Annual CTRC-AACR San Antonio Breast Cancer Symposium (SABCS), an international scientific symposium for scientists and clinicians in breast cancer.

"These data represent an important milestone in the treatment of women with breast cancer. For the first time, we are seeing suggested survival benefit with aromatase inhibitor therapy for five years compared with tamoxifen for the same time period," said Henning T Mouridsen, professor of Oncology, Copenhagen University Hospital and one of the investigators of the BIG 1-98 trial. "The potential reduction in the risk of death that we are seeing with letrozole in the adjuvant setting may be a positive result of letrozole's early and sustained reduction in the risk of recurrence and distant metastases."

BIG 1-98 is the only clinical trial designed to explore both a head-to-head comparison of an aromatase inhibitor with tamoxifen during the first five years following breast cancer surgery and the sequencing of both agents to determine the most effective approach to minimizing the risk of recurrence. In the initial adjuvant setting, Femara is the only aromatase inhibitor to have demonstrated an early significant reduction in distant metastases versus tamoxifen, at a median duration of follow-up of 26 months.
Beyond the potential survival benefit or 13 per cent (P=0.08, HR=0.87, 95% CI: 0.75-1.02) reduction in risk of death for Femara patients seen in the ITT analysis, Femara demonstrated significant long-term benefit in reducing the risk of disease free survival events by 12 per cent (P=0.03, HR=0.88, 95% CI: 0.78-0.99) and reducing the risk of distant metastases by 15% (P=0.05, HR=0.85, 95% CI: 0.72-1.00) compared with tamoxifen.

"Femara has consistently demonstrated remarkable results and these data reaffirm the benefit of Femara for postmenopausal women with early-stage breast cancer," said Alessandro Riva, executive vice president, head of Global Development at Novartis Oncology. "The survival data shown may offer new promise for breast cancer patients."

Also presented at the meeting were results from the Sequential Treatment Analysis (STA) of BIG 1-98 that support the benefit of starting adjuvant treatment with five years of Femara after surgery. This analysis (from randomization) revealed that sequencing hormone therapy following surgery is not superior to five years of Femara alone.

The five-year disease-free survival rates for the three groups of patients in the STA were 87.9 per cent for those patients receiving Femara only, 86.2 per cent for those patients receiving two years of tamoxifen followed by three years of Femara and 87.6 per cent for those patients receiving two years of Femara followed by three years of tamoxifen. The study investigators conclude that sequential treatment does not improve disease free survival compared with Femara alone.