The BOLERO-2 trial: the addition of everolimus to exemestane in the treatment of postmenopausal hormone receptor-positive advanced breast cancer

Future Oncol. 2012 Jun;8(6):651-7. doi: 10.2217/fon.12.49.


The combination of the mTOR inhibitor everolimus with the aromatase inhibitor exemestane was evaluated in the randomized Phase III BOLERO-2 trial. Research has indicated that aberrant signaling through the mTOR pathway is associated with resistance to endocrine therapies. The BOLERO-2 trial examined the effects on progression-free survival of the addition of everolimus to exemestane in a patient population of postmenopausal, hormone receptor-positive, advanced breast cancer. At the interim analysis, the median progression-free survival assessed by local investigators was 6.9 months for everolimus plus exemestane versus 2.8 months for placebo plus exemestane (hazard ratio: 0.43; p < 0.001), and by central assessment was 10.6 versus 4.1 months, respectively (hazard ratio: 0.36; p < 0.001). The everolimus plus exemestane arm showed greater number of grade 3 and 4 adverse events. This study suggests that the addition of everolimus to exemestane is a potential viable treatment option for this patient population.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Androstadienes / administration & dosage
  • Androstadienes / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Everolimus
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Postmenopause
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / genetics
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • Treatment Outcome


  • Androstadienes
  • Receptors, Estrogen
  • Everolimus
  • Receptor, ErbB-2
  • exemestane
  • Sirolimus