Switching From Tamoxifen to Letrozole Improves Breast Cancer Survival

June 3, 2007
Mark L. Fuerst

Internal Medicine World Report, August 2006, Volume 0, Issue 0

ATLANTA—Postmenopausal women with breast cancer who switch from tamoxifen (Nolvadex) to letrozole (Femara) have a dramatically reduced risk of recurrence and distant metastasis, and they live longer, as evidenced by new data presented at the American Society of Clinical Oncology annual meeting.

An updated analysis of the landmark MA-17 trial showed that extended adjuvant use of letrozole, even after years without anticancer therapy, provided significant benefit for 2 populations at high risk of recurrence-women whose cancer has already spread to the lymph nodes at diagnosis (node positive), and women who received chemotherapy after surgery.

In this phase 3, double-blind, multicenter trial, 5187 postmenopausal women with early breast cancer who were free of disease after 5 years of tamoxifen therapy were randomly assigned to receive 5 years of letrozole treatment or placebo. The trial was unblinded when the first interim analysis in 2003 showed letrozole lowered the risk of recurrence by 42% compared with placebo. Of the 2268 participants originally assigned to placebo who were then offered letrozole, 1655 women elected to switch to letrozole, while 613 chose not to pursue further treatment.

Women who used letrozole for 5 years after tamoxifen significantly improved in all end points.

After blinding, a numerical (but not significant) trend was seen toward more clinical fractures in the letrozole-treated patients compared with placebo recipients. New diagnoses of osteoporosis were also more common in the letrozole group.

This study represents the first time that an aromatase inhibitor has demonstrated benefits when therapy is started up to 5 years after a patient finished taking tamoxifen, said Nicholas Robert, MD, of Fairfax Northern Virginia Hematology Oncology, Fairfax.

Overall, women who switched from placebo to letrozole had a:

• 69% reduction in recurrence

• 72% reduction in distant metastases

• 47% reduction in mortality.

“We recognize that the 2 groups compared postblinding had different baseline characteristics. But if anything, the women who elected to switch to letrozole had a higher risk of disease recurrence,” Dr Robert said.