Exemestane Is Superior to Tamoxifen in Postmenopausal Breast Cancer

San Antonio, TX — Postmenopausal women with hormone receptor-positive breast cancer who switch to exemestane (Aromasin) after taking tamoxifen for 2 to 3 years have superior outcomes compared with women who stay on tamoxifen for 5 years, according to an updated analysis of the Intergroup Exemestane Study (IES) presented at the 2009 San Antonio Breast Cancer Symposium.

“These women [switched to exemestane] have real improvements that persist at least 9 years, which is 11 years from the time of diagnosis,” stated Judith Bliss, MD, The Institute of Cancer Research, Sutton, U.K. “They have a modest but persistent improvement in overall survival and a modest reduction in distant recurrence,” she added.

The study included 4724 patients recruited from 366 sites in 37 countries; women were enrolled from 1998 to 2003. Slightly less than 50% of patients (44.2%) had node-positive disease; one third had adjuvant chemotherapy; mean age was 64. The analysis presented here was based on 91 months of follow-up.

Overall survival (OS) in the 4599 women with estrogen receptor-positive and estrogen receptor-unknown status was superior in the patients who switched to exemestane. The absolute difference in OS favoring exemestane was 1.4% at 5 years, and 2.4% at 8 years (

= .04). Disease-free survival (DFS) was highly statistically significant in favor of exemestane: at 5 years, the absolute difference in DFS was 3%, and at 8 years, it was 4.4% (

= .0009).

PP

The annual (DFS) event rate (breast cancer recurrence, new primary cancer, or death) was 4% per year. “There is no evidence that the event rate diminishes more than 10 years from diagnosis,” Dr Bliss told listeners. The risk for local recurrence was .5% per year, and the risk of distant recurrence was 2.5% per year.

Inter-current deaths are rare, she explained, and as they become more common over time, they can blunt the difference between treatment groups. “Breast-cancer-free survival is a more sensitive estimate of differences,” she said.

At 5 years, the absolute difference in breast-cancer-free survival favoring exemestane was 2.8%, and at 8 years, it was 4.1% (

= .001). While on treatment, the risk of a breast cancer event was reduced by 40% in those who switched to exemestane. In the post-treatment follow-up phase, the risk of a breast cancer event rate was reduced by 16% in exemestane users.

P

All subgroup analyses for the breast-cancer-free survival endpoint favored exemestane. Looking at time to distant recurrence, which is strongly associated with breast cancer mortality, exemestane was significantly superior to tamoxifen (

= .01). There were 319 distant recurrences in those who switched to exemestane versus 370 in the tamoxifen group.

P

In an exploratory analysis of sites of first reported distant recurrence, exemestane appeared to have a benefit in preventing metastasis involving bone. Bone-only metastases occurred in 75 patients in the exemestane group versus 109 in the tamoxifen group. There were 147 distant recurrences that included bone in the exemestane group versus 192 in the tamoxifen group. Dr Bliss said this purported benefit of exemestane was “wildly speculative” and hypothesis generating.

Another surprising finding was an increase in the number of non-breast primary cancers in the tamoxifen group: 106 versus 159, respectively. “Exemestane has an unexpected lower number of reported non-breast second primary cancers,” she noted. Looking at age at randomization, the evidence for non-primary-breast-cancers suggests that there are true secondary primary cancers and not recurrences, she added.

The findings regarding the metastases involving the bone and the smaller number of non-breast-cancer second primary cancers require further validation, she said.

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SABCS Abstract 12