Aromatase inhibitors alone or in sequence with tamoxifen - Clinical Evaluation of the BIG 1-98 trial

Abstract

Background: BIG 1-98 is a randomized Phase III, double-blind trial that compared tamoxifen and letrozole monotherapy and sequences of both with letrozole monotherapy. Results: At a median follow-up of 71 months, disease-free survival (DFS) was not significantly improved in either sequential arm compared with letrozole. At a median follow-up of 76 months, there was a statistically significant improvement observed for DFS (HR = 0.88; 95% CI 0.78 – 0.99 in the intention-to-treat analysis) and a trend towards improved overall survival (HR = 0.87; 95% CI 0.75 – 1.02) for letrozole compared with tamoxifen. Discussion: Sequential therapy is not superior to letrozole monotherapy. Lack of statistical significance does not imply that patients should be switched to tamoxifen after 2 years of an aromatase inhibitor (AI). Long-term data from the ATAC trial shows a significant carry-over effect after 5 years of an AI; we do not have such data for 2 years of an AI. Interpretation of the monotherapy results are confounded by the fact that 25% of patients randomized to tamoxifen crossed over to letrozole after the initial BIG 1-98 results were reported in 2005. Conclusion: This is the second large Phase III trial to show that upfront AI use is superior to tamoxifen.

Keywords::

• breast cancer
• letrozole
• sequential therapy
• tamoxifen