Clinical Trial

Breast Cancer Research and Treatment

, Volume 143, Issue 3, pp 459-467

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Everolimus plus exemestane as first-line therapy in HR+, HER2 advanced breast cancer in BOLERO-2

  • J. Thaddeus BeckAffiliated withHighlands Oncology Group Email author 
  • , Gabriel N. HortobagyiAffiliated withThe University of Texas M.D. Anderson Cancer Center
  • , Mario CamponeAffiliated withInstitut de Cancérologie de l’Ouest - Rene Gauducheau Centre de Recherche en Cancérologie
  • , Fabienne LebrunAffiliated withInstitut Jules Bordet
  • , Ines DeleuAffiliated withAZ Nikolaas
  • , Hope S. RugoAffiliated withUniversity of California, San Francisco Helen Diller Family Comprehensive Cancer Center
  • , Barbara PistilliAffiliated withOspedale di Macerata
  • , Norikazu MasudaAffiliated withDepartment of Surgery, Breast Oncology, Osaka National Hospital
  • , Lowell HartAffiliated withFlorida Cancer Specialists
    • , Bohuslav MelicharAffiliated withPalacky University Medical School and Teaching Hospital
    • , Shaker DakhilAffiliated withCancer Center of Kansas
    • , Matthias GeberthAffiliated withPGO-Mannheim, Schwerpunktpraxis für Gynäkologische Onkologie
    • , Martina NunziAffiliated withHospital Santa Maria of Terni
    • , Daniel Y. C. HengAffiliated withTom Baker Cancer Center, University of Calgary
    • , Thomas BrechenmacherAffiliated withNovartis Pharma SAS
    • , Mona El-HashimyAffiliated withNovartis Pharmaceuticals Corporation
    • , Shyanne DoumaAffiliated withNovartis Pharmaceuticals Corporation
    • , Francois RingeisenAffiliated withNovartis Pharma AG
    • , Martine PiccartAffiliated withInstitut Jules Bordet


The present exploratory analysis examined the efficacy, safety, and quality-of-life effects of everolimus (EVE) + exemestane (EXE) in the subgroup of patients in BOLERO-2 whose last treatment before study entry was in the (neo)adjuvant setting. In BOLERO-2, patients with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2) advanced breast cancer recurring/progressing after a nonsteroidal aromatase inhibitor (NSAI) were randomly assigned (2:1) to receive EVE (10 mg/day) + EXE (25 mg/day) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local assessment. Overall, 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37). Median PFS by local investigator assessment nearly tripled to 11.5 months with EVE + EXE from 4.1 months with PBO + EXE (hazard ratio = 0.39; 95 % CI 0.25–0.62), while maintaining quality of life. This was confirmed by central assessment (15.2 vs 4.2 months; hazard ratio = 0.32; 95 % CI 0.18–0.57). The marked PFS improvement in patients receiving EVE + EXE as first-line therapy for disease recurrence during or after (neo)adjuvant NSAI therapy supports the efficacy of this combination in the first-line setting. Furthermore, the results highlight the potential benefit of early introduction of EVE + EXE in the management of HR+, HER2 advanced breast cancer in postmenopausal patients.


BOLERO-2 Breast cancer Everolimus First-line therapy Metastatic disease mTOR inhibition