Safety and efficacy of everolimus (EVE) plus exemestane (EXE) in postmenopausal women with locally advanced or metastatic breast cancer: final results from EVEREXES

Breast Cancer Res Treat. 2021 Jul;188(1):77-89. doi: 10.1007/s10549-021-06173-z. Epub 2021 Mar 16.


Background: This study was conducted to collect clinical safety, tolerability, and efficacy data with the use of everolimus (EVE) combined with exemestane (EXE) in patients with advanced breast cancer (ABC).

Methods: The EVEREXES trial initiated in 2012, provided early access to the first dual blockade treatment with EVE + EXE in patients with HR+, HER2 - ABC in Asia and other emerging growth countries. Postmenopausal women with HR+, HER2 - ABC who had documented recurrence or progression, following a nonsteroidal aromatase inhibitor therapy, were treated with EVE (10 mg/day) + EXE (25 mg/day) orally.

Results: A total of 235 patients received ≥ 1 dose of study medication. At the end of the study, all patients ceased the treatment. Disease progression (66.0%) was the primary reason of discontinuation. The most common AEs (≥ 20%) were stomatitis, decreased appetite, hyperglycemia, rash, aspartate aminotransferase increased, anemia, alanine aminotransferase increased, cough, and fatigue. No new safety concerns were identified in the current study. Median progression-free survival (PFS) in the Asian subset was similar to that of the overall population (9.3 months in both groups). Confirmed overall response rate (ORR) was achieved for 19.6% of the patients. Efficacy of EVE + EXE across subgroups (prior CT, line of treatment, and presence of visceral metastases) was maintained.

Conclusion: The safety and efficacy results from EVEREXES trial are consistent to data previously reported in BOLERO-2. These results support that EVE + EXE could be a viable treatment option for the postmenopausal women with HR+, HER2 - ABC in Asian region.

Keywords: Breast Cancer; EVEREXES; Everolimus; Exemestane; HER2 −; HR +; Mammalian target of rapamycin (mTOR).

MeSH terms

  • Androstadienes / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols
  • Asia
  • Breast Neoplasms* / drug therapy
  • Everolimus* / therapeutic use
  • Female
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Postmenopause
  • Receptor, ErbB-2
  • Sirolimus / therapeutic use


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