Exemestane versus Tamoxifen for Women with Premenopausal Breast Cancer

Chicago—After a median follow-up of 5.7 years, an analysis of 2 phase 3, randomized studies found that premenopausal women with hormone receptor-positive (HR+) early breast cancer who received exemestane plus ovarian function suppression (OFS) had a significant improvement in disease-free survival compared with a group who received tamoxifen plus OFS.

At 5 years, the disease-free survival rate was 91.1% in the exemestane group and 87.3% in the tamoxifen group (hazard ratio [HR], 0.72; P=.0002). Disease-free survival included invasive local, regional, and distant recurrences; invasive contralateral breast cancer; second malignancies; or death.

The exemestane group also had a significant improvement in breast cancer-free interval at 5 years (92.8% vs 88.8%, respectively; HR, 0.66; P<.0001) and distant recurrence-free interval at 5 years (93.8% vs 92%, respectively; HR, 0.78; P=.02). There was no significant difference in overall survival at 5 years (95.9% vs 96.9%, respectively; HR, 1.14; P=.37).

Olivia Pagani, MD, the study’s lead author, presented the results during a plenary session at the ASCO meeting. The findings were simultaneously published in New England Journal of Medicine [2014; DOI:10.1056/NEJMoa1404037]. The study was funded by Pfizer Inc., Ipsen, and the National Cancer Institute. Dr. Pagani recommended a long-term follow-up of the women to assess survival and fertility.

Dr. Pagani said the results were similar in both trials and in women who received chemotherapy or did not have chemotherapy. She added that the relative and absolute differences in disease-free survival between the groups at 5 years compared favorably with the Breast International Group 1-98 study and the ATAC [Arimidex, Tamoxifen, Alone or in Combination] trial. Those trials compared aromatase inhibitors with tamoxifen in postmenopausal women.

Although treatment with tamoxifen for 5 years is considered the standard of care for premenopausal women with HR+ early breast cancer, Dr. Pagani said the optimal adjuvant endocrine therapy is uncertain. OFS is sometimes used, but it is more common outside of the United States. Exemestane is an FDA-approved, oral aromatase inhibitor taken once daily after a meal.

The SOFT [Suppression of Ovarian Function Trial] and TEXT [Tamoxifen and Exemestane Trial] studies were conducted simultaneously beginning in 2003. They were coordinated by the International Breast Cancer Study Group in collaboration with the Breast International Group and the North American Breast Cancer Group. The trials were designed to accommodate international variations in treatment strategies, according to Dr. Pagani.

Women were enrolled at 510 centers in 27 countries between November 2003 and April 2011. The median age at randomization was 43 years. In addition, 42% of women had node-positive disease, 36% had tumors larger than 2 cm, and 12% had human epidermal growth factor receptor 2 positive disease.

The TEXT trial included 2672 patients who were randomized to receive 5 years of 20 mg tamoxifen daily plus OFS or 25 mg exemestane daily plus OFS, while the SOFT trial included 3066 patients who were randomized to receive 5 years of 20 mg tamoxifen alone daily, 20 mg tamoxifen daily plus OFS, or 25 mg exemestane daily plus OFS. In both trials, the use of chemotherapy was optional. More than half of the women received chemotherapy after randomization in TEXT or before randomization in SOFT. Patients were also allowed to take trastuzumab.

Dr. Pagani discussed the results of the joint analysis of TEXT and SOFT studies that included 4690 patients. She did not analyze patients in the SOFT trial who were in the tamoxifen alone group. The adverse events associated with exemestane plus OFS were comparable with those in other aromatase inhibitors in postmenopausal women, according to Dr. Pagani.

As the trials progressed, Dr. Pagani said the authors observed a much lower disease-free survival event rate than anticipated. In 2011, they amended the protocols and decided that the joint analysis of SOFT and TEXT would become the primary analysis. At the time of the presentation, they had no knowledge of efficacy data. They set the data cut-off for the third quarter of 2013, when the median follow-up exceeded 5 years. They decided to not have any interim analyses.—Tim Casey