The US Food and Drug Administration has granted priority review to letrozole as adjuvant treatment for postmenopausal women with hormone receptor-positive early breast cancer because the drug had significantly better efficacy than tamoxifen for women with node-positive disease and women who received chemotherapy. Letrozole also demonstrated significantly reduced risk for distant metastases compared with tamoxifen.

If approved for this new indication, letrozole will become the only breast cancer treatment approved in the US to significantly reduce risk of recurrence in both the adjuvant setting and as extended adjuvant treatment following standard tamoxifen therapy.

The FDA submission is based on data from the Breast International Group (BIG) 1-98 study, a Phase III, randomized, double-blind study that compared the safety and efficacy of adjuvant letrozole versus tamoxifen in more than 8,000 postmenopausal women with hormone receptor-positive early breast cancer.

The overall results of BIG 1-98 demonstrated that at a median follow-up of 26 months, letrozole prolonged disease-free survival by reducing risk of recurrence by an additional 21 percent (p=0.002) over the reduction offered by tamoxifen. Women who were treated with letrozole experienced a 27-percent reduction in the risk for distant metastases compared with tamoxifen (p=0.001). Letrozole also provided a 14-percent reduction in the risk of death, although this did not reach statistical significance (p=0.155).

In two separate pre-planned subset analyses, letrozole also reduced risk of cancer recurrence by 29 percent among patients whose initial cancer was node-positive and by 30 percent in those who had received chemotherapy, two groups that are at increased risk of recurrence. Additionally, in node-positive patients and in patients who received adjuvant chemotherapy, the risk of distant metastases was reduced by more than 30 percent with letrozole compared to tamoxifen.

BIG 1-98 was the only clinical trial designed to incorporate both a head-to-head comparison of letrozole with tamoxifen during the first five years following breast cancer surgery and a sequencing of both agents to determine the most effective approach to minimizing risk of recurrence. Patients were randomized to the following arms: tamoxifen for five years, letrozole for five years, tamoxifen for two years followed by letrozole for three years, and letrozole for two years followed by tamoxifen for three years. BIG 1-98 was conducted by the International Breast Cancer Study Group (IBCSG).