Exemestane Plus Ovarian Suppression Demonstrates Sustained Higher Rates of Disease Free Survival in Premenopausal Women with Breast Cancer

Background

• The International Breast Cancer Study Group initiated two randomized trials,
  • SOFT Trial - The Suppression of Ovarian Function Trial
  • TEXT Trial - The Tamoxifen and Exemestane Trial
• SOFT investigated the role of ovarian suppression (OS) and role of aromatse inhibitor (exemestane) in premenopausal women with hormone-receptor- positive early breast cancer
• TEXT trial investigated the efficacy of exemestane (E) / tamoxifen (T) in women treated with ovarian suppression

• Exemestane plus ovarian suppression resulted in significantly higher rates of disease-free survival than the rates with tamoxifen plus ovarian suppression according to results of the combined analysis of SOFT and TEXT after a median follow-up of 5.7 years.

Aim

This analysis reported results of a prespecified updated analysis of SOFT and the combined analysis of data from SOFT and TEXT after a median follow-up of 8 and 9 years, respectively.

Method

• The combined analysis of SOFT and TEXT compared  exemestane plus ovarian suppression and tamoxifen plus ovarian suppression  and included 4690 women
• In SOFT Trial , 3047 women were included in the intention-to-treat population for the two pairwise comparisons of tamoxifen alone versus tamoxifen plus ovarian suppression and exemestane plus ovarian suppression
• The primary end point in the time-to-event analysis was disease-free survival, which was defined as survival free of the first occurrence of one of the following: invasive recurrence of breast cancer (local, regional, or distant), invasive contralateral breast cancer, a second (nonbreast) invasive cancer, or death without recurrence or a second cancer.

Results

Hazards ratio (HR)for overall survival ; E+OS =0.85;T+OS=0.67 , HR for Freedom from distant recurrence ; E+OS= 0.73;T+OS=0.86, HR for Disease free survival; E+OS=0.65; T+OS=0.76

• Grade 3 or higher adverse events were reported in
  •  Tamoxifen alone group (24.6%), tamoxifen–ovarian suppression group (31.0%) and exemestane–ovarian suppression group (32.3%)

Conclusion

• In combined analysis of SOFT and TEXT trial , after a median of follow up of more than 8 years treatment with exemestane plus ovarian suppression resulted in sustained and consistently higher rates of disease-free survival and freedom from distant recurrence than the rates with tamoxifen plus ovarian suppression
• The addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free among premenopausal women than tamoxifen alone

NEJM June 4, 2018 .DOI: 10.1056/NEJMoa1803164