Original Research

Advances in Therapy

, Volume 30, Issue 10, pp 870-884

First online:

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

Everolimus Plus Exemestane in Postmenopausal Patients with HR+ Breast Cancer: BOLERO-2 Final Progression-Free Survival Analysis

  • Denise A. YardleyAffiliated withSarah Cannon Research Institute and Tennessee Oncology, PLLC Email author 
  • , Shinzaburo NoguchiAffiliated withDepartment of Breast and Endocrine Surgery, Osaka University
  • , Kathleen I. PritchardAffiliated withSunnybrook Odette Cancer Centre and the University of Toronto
  • , Howard A. BurrisIIIAffiliated withSarah Cannon Research Institute and Tennessee Oncology, PLLC
  • , José BaselgaAffiliated withMemorial Sloan-Kettering Cancer Center
  • , Michael GnantAffiliated withDepartment of Surgery, Comprehensive Cancer Center, Medical University of Vienna
  • , Gabriel N. HortobagyiAffiliated withThe University of Texas MD Anderson Cancer Center
  • , Mario CamponeAffiliated withInstitut de Cancérologie de l’Ouest, René Gauducheau, Centre de Recherche en Cancérologie
  • , Barbara PistilliAffiliated withDepartment of Medical Oncology, Ospedale di Macerata
    • , Martine PiccartAffiliated withInstitut Jules Bordet, Université Libre de Bruxelles
    • , Bohuslav MelicharAffiliated withDepartment of Oncology, Palacky University Medical School and Teaching Hospital
    • , Katarina PetrakovaAffiliated withMasaryk Memorial Cancer Institute
    • , Francis P. ArenaAffiliated withNYU Langone Arena Oncology, P.C.
    • , Frans ErdkampAffiliated withDepartment of Medical Oncology, Orbis Medical Center
    • , Wael A. HarbAffiliated withHorizon Oncology
    • , Wentao FengAffiliated withNovartis Pharmaceuticals Corporation
    • , Ayelet CahanaAffiliated withNovartis Pharmaceuticals Corporation
    • , Tetiana TaranAffiliated withNovartis Pharmaceuticals Corporation
    • , David LebwohlAffiliated withNovartis Pharmaceuticals Corporation
    • , Hope S. RugoAffiliated withUCSF Helen Diller Family Comprehensive Cancer Center



Effective treatments for hormone-receptor-positive (HR+) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population.


BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR+ advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints.


Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38–0.54); log-rank P < 0.0001; central review: 11.0 versus 4.1 months, respectively; hazard ratio = 0.38 (95% confidence interval 0.31–0.48); log-rank P < 0.0001] in the overall population and in all prospectively defined subgroups, including patients with visceral metastases, patients with recurrence during or within 12 months of completion of adjuvant therapy, and irrespective of age. The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials.


The addition of everolimus to exemestane markedly prolonged PFS in patients with HR+ advanced BC with disease recurrence/progression following prior NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655.


Advanced breast cancer Everolimus Exemestane Hormone receptor positive Nonsteroidal aromatase inhibitors Oncology Postmenopausal Progression-free survival