Studies Demonstrate Effectiveness of Exemestane in Early Stage Breast Cancer

Updated data from IES (Intergroup Exemestane Study) showed that sequencing therapy with tamoxifen followed by exemestane (Aromasin) prolonged disease-free survival (DFS) and overall survival (OS) in postmenopausal women with early stage breast cancer. More than 4700 women have been followed for a median of 91 months in what investigators say is the “longest follow-up of endocrine treatment in the adjuvant switch setting.”

The women received a total of 5 years of therapy in this randomized trial; 2352 women received tamoxifen for 2 or 3 years followed by exemestane for the remainder of the 5-year period; the other 2372 patients took tamoxifen for 5 years. The majority of patients (97%) were estrogen-receptor positive (ER+)/unknown.

Compared with women who took tamoxifen for the entire 5-year period, women in the sequencing arm of the trial had an 18% reduction in the risk of DFS events, which included local or distant recurrence, development of contralateral tumors, and death (from any cause). In the intent-to-treat (ITT) population, risk of DFS events was reduced by 16% in the sequencing group (P = .002). Women with ER+/unknown tumors who switched from tamoxifen to exemestane were 14% less likely to die during the follow-up period compared with women who took only tamoxifen (P = .04). The relative risk of reduction in death was 11% for the ITT population.

These findings are significant and consistent with results presented from IES at 55.7 months’ follow-up, demonstrating that the benefits associated with exemestane persist long after treatment discontinuation. Charles Coombes, MD (pictured right), head of oncology at Imperial College in the United Kingdom served as lead investigator of the study. He told Oncology & Biotech News that the findings should affect the treatment of postmenopausal women with early stage breast cancer at the community practice level. “If they have been taking tamoxifen for 2 to 3 years, they should switch to exemestane,” he said. He recommended that oncologists monitor bone mineral density and blood pressure in patients taking exemestane, which are some of the more common adverse affects associated with this medication. ECCO/ESMO Abstract 5010

Data from the phase III TEAM (Tamoxifen Exemestane Adjuvant Multinational) trial was also presented at the ECCO 15 - ESMO 34 Joint Congress. Cornelis van de Velde, MD, PhD, a professor of surgery at Leiden University Medical Center, the Netherlands, reported that in a head-to-head comparison of initial adjuvant therapy with tamoxifen versus exemestane in postmenopausal women with hormone receptor-positive breast cancer, exemestane was determined to be safer and more effective.

Researchers analyzed data for 9779 women with breast cancer from several countries, including the United States. Women who received initial therapy with exemestane had an 11% reduction in the risk of DFS events and improved recurrence-free survival. In addition, the rate of noncompliance was higher for the women randomized to take tamoxifen, at 19.8% compared with 12.9% for the exemestane group. Dr van de Velde cautioned that the relatively short 2.75-year follow-up period made it hard to determine the significance of these findings. The improvement in reduced risk of DFS was significant, however, for women >70 years of age and women with N1 tumors.

This is the second large study comparing an aromatase inhibitor against tamoxifen that has reported improved safety and efficacy with the aromatase inhibitor. In August, the BIG I-98 study published updated data in the New England Journal of Medicine showing 5 years of letrozole (Femara) improved DFS rates compared with tamoxifen alone or tamoxifen/leptosome sequencing. ECCO/ESMO Abstract 2BA