BIG 1-98: Sequences of tamoxifen and letrozole not superior to letrozole monotherapy

San Antonio Breast Cancer Symposium

SAN ANTONIO — Sequential treatments of letrozole and tamoxifen did not demonstrate superior results in DFS, OS and time to distant recurrence compared with letrozole monotherapy, according to the results of a phase-3 study presented at the San Antonio Breast Cancer Conference.

Alan Coates, MD, clinical professor of public health in the School of Public Health at The University of Sydney, and his colleagues in the BIG 1-98 Collaborative Group and the International Breast Cancer Study Group, evaluated 6,182 postmenopausal women with receptor-positive breast cancer in the four-arm trial. They randomly assigned 1,548 women to treatment with tamoxifen for five years; 1,546 women to letrozole for five years; 1,548 to a sequence of tamoxifen for two years and letrozole for three years; and 1,540 to a sequence of letrozole for two years and tamoxifen for three years.

At a median follow-up of 76 months, the researchers found that neither sequence showed improvement over five years of letrozole monotherapy (see chart).

Coates also presented updated data for the monotherapy results, originally released in 2005. At a median follow-up of 76 months, letrozole demonstrated superior results over tamoxifen in the intent-to-treat population for DFS (HR=0.88; 95% CI, 0.78-0.99), OS (HR=0.87; 95% CI, 0.75-1.02) and time to distant recurrence (HR=0.85; 95% CI, 0.72-1.00).

Despite these findings, Coates pointed out that, although neither of the sequence therapies were superior to letrozole therapy, the differences were not statistically significant. “It looks very clear that you can indeed switch back from letrozole to tamoxifen if the side effects of letrozole prove to be an indication for doing that,” he said. “Some women find these aromatase inhibitors hard to take, not only because of menopausal symptoms, but also because of arthralgia and myalgia. If women are worried about doing themselves a disservice by switching after a couple of years, then I think these data are reassuring that they do not need to worry that a switch back to tamoxifen would compromise their outcome in any way.” – by Tina DiMarcantonio

Sequential Treatments vs. Letrozole Monotherapy

	Tamoxifen to Letrozole Sequence vs. Letrozole	Letrozole to Tamoxifen Sequence vs. Letrozole
DFS	HR=1.05 (99% CI, 0.84-1.32)	HR=0.96 (99% CI, 0.76-1.21)
OS	HR=1.13 (99% CI, 0.83-1.53)	HR=0.90 (99% CI, 0.65-1.24)
Time to distant recurrence	HR=1.22 (99% CI, 0.88-1.69)	HR=1.05 (99% CI, 0.75-1.47)

For more information:

Coates A. #13. Presented at: the 31st Annual CTRC-AACR San Antonio Breast Cancer Symposium; Dec. 10-14, 2008; San Antonio.