Letrozole: The treatment profile, the remaining questions

The primary endpoint, disease-free survival, significantly improved with letrozole therapy compared with placebo.

The study was halted and patients were informed of the results even before this initial report was published, less than halfway into the trial period.

Women who match the study group criteria should be considered for letrozole treatment, although the trial’s early termination leaves optimal duration of treatment undefined and the question of long-term toxicity unanswered, the investigators stated in their report.Raw Letrozole powder

Background

In women with hormone-dependent breast cancer, tamoxifen therapy prolongs postoperative disease-free and overall survival for 5 years, but has not been found beneficial beyond the 5-year mark. This Canadian-led international clinical trial analyzed the effects of treatment with letrozole in years 5 through 10 after diagnosis. The research question was whether the aromatase inhibitor letrozole, by suppressing estrogen production, would improve the outcome after the initial 5-year course of tamoxifen. Estrogen is thought to stimulate development and growth of breast cancer.

Methods And Results

This double-blind, placebo-controlled trial enrolled 5,157 post-menopausal women with primary breast cancer who had completed 4.5 to 6 years of adjuvant tamoxifen therapy less than 3 months before study enrollment. Of this group, 2,575 were randomized to receive 2.5 mg oral letrozole daily for 5 years; the remaining 2,582 received placebo. The study included women in the United States, Canada, and Europe. All patients were to undergo clinical evaluation twice in the first year and annually thereafter.

At the first interim analysis, after a median follow-up of 2.4 years, results in the letrozole group were significantly more favorable in these respects:

Greater disease-free survival: 93% versus 87%.
Lower primary cancer recurrence rate: 2.4% versus 4.1%.
Lower rate of new contralateral breast cancers: 0.5% versus 1%.