Prior research has shown that letrozole monotherapy is more effective than tamoxifen monotherapy in improving disease-free survival in postmenopausal women with receptor-positive early breast cancer. Whether survival might be improved further by giving the two drugs in sequence was unclear.
To investigate, Dr. Henning Mouridsen of Rigshospitalet in Copenhagen, with colleagues from the Breast International Group 1-98, assessed the outcomes of 6182 women who were randomized to receive letrozole, tamoxifen, letrozole then tamoxifen (2, 3 years), or tamoxifen then letrozole (2, 3 years) for 5 years total.
Additionally, the researchers examined the examined letrozole versus tamoxifen monotherapy in 4922 women.
During a median follow-up period of 71 months, disease-free survival in the sequence groups was no better (or worse) than that seen in the letrozole monotherapy group. In fact, compared to the letrozole monotherapy group, more early relapses were noted in women who received tamoxifen followed by letrozole.
As for the monotherapy comparison, the findings agreed with previous reports showing that disease-free survival is better with letrozole than with tamoxifen. There was also a trend toward better overall survival with letrozole (p = 0.08).
Adverse events in all of the groups were consistent with previous reports, the authors note.
“The safety and efficacy results add to the information that supports the use of adjuvant endocrine therapy with letrozole in postmenopausal women with endocrine-responsive early breast cancer,” the team concludes.
N Engl J Med 2009;361:766-776.