Adjuvant exemestane with ovarian suppression in premenopausal breast cancer

N Engl J Med. 2014 Jul 10;371(2):107-18. doi: 10.1056/NEJMoa1404037. Epub 2014 Jun 1.

Abstract

Background: Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer.

Methods: In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials.

Results: After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women.

Conclusions: In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.).

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Androstadienes / adverse effects
  • Androstadienes / therapeutic use*
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Aromatase Inhibitors / adverse effects
  • Aromatase Inhibitors / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / radiotherapy
  • Breast Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Estradiol / blood
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Mastectomy
  • Middle Aged
  • Osteoporosis / chemically induced
  • Premenopause
  • Quality of Life
  • Tamoxifen / adverse effects
  • Tamoxifen / therapeutic use*
  • Triptorelin Pamoate / adverse effects
  • Triptorelin Pamoate / therapeutic use*

Substances

  • Androstadienes
  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Triptorelin Pamoate
  • Tamoxifen
  • Estradiol
  • exemestane

Associated data

  • ClinicalTrials.gov/NCT00066690
  • ClinicalTrials.gov/NCT00066703