The aromatase inhibitor letrozole compares favorably with tamoxifen as an adjuvant treatment for hormone receptor-positive breast cancer in postmenopausal women, reported Dr. Beat Thürlimann and associates in the Breast International Group 1–98 trial.
Interim results of this multinational phase III clinical trial at the 2-year mark “indicate that letrozole is an effective option for standard adjuvant therapy, with a relatively favorable safety profile,” compared with tamoxifen. Letrozole was superior to tamoxifen in decreasing the risk of distant metastases, said Dr. Thürlimann of the Swiss Group for Clinical Cancer Research and the Senology Center of Eastern Switzerland, Kantonsspital, St. Gallen, and associates.
Letrozole (Femara) was approved in December for adjuvant treatment of early hormone-sensitive breast cancer in postmenopausal women, based on the results of the BIG 1–98 trial. The trial involved 8,010 postmenopausal women with invasive breast cancer that was positive for estrogen receptors, progesterone receptors, or both. The women were randomly assigned to receive one of three regimens after surgery: monotherapy with either letrozole or tamoxifen for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years.
This planned interim analysis compared outcomes after a median of 26 months for the 4,003 women assigned to letrozole initially with those of the 4,007 assigned to tamoxifen initially (New Engl. J. Med. 2005;353:2747–57).
Disease-free survival was significantly greater in the letrozole group, and the drug was particularly effective in reducing recurrences at distant sites. The 5-year estimates of disease-free survival were 84% in the letrozole group and 81.4% in the tamoxifen group.
Subgroup analysis showed that letrozole was superior to tamoxifen for the subset of patients who received chemotherapy, the subset who did not receive radiotherapy, and the subset with positive axillary nodes.
Letrozole significantly decreased the cumulative incidence of breast cancer relapse, compared with tamoxifen. “This difference became evident 1 year after randomization, and there was an absolute difference of 3.4 percentage points at 5 years,” they noted.
More patients in the letrozole group than in the tamoxifen group reported adverse events, but the incidence of life-threatening adverse events was 1.7% for both. Bone fractures were more frequent with letrozole (5.7% vs. 4.0%), and the interval before sustaining a fracture was significantly shorter.
Letrozole was associated with fewer thromboembolic events (1.5% vs. 3.5%), episodes of vaginal bleeding (3.3% vs. 6.6%), endometrial biopsies (2.3% vs. 9.1%), and invasive endometrial cancers (0.1% vs. 0.3%).
The overall incidence of adverse cardiovascular events was similar in the two groups (letrozole, 3.7%; tamoxifen, 4.2%), but more women on letrozole had severe cardiac events (2.1% vs. 1.1%).
This study was funded in part by Novartis Pharmaceuticals Corp., the manufacturer of letrozole (Femara).