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Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole (BOLERO-2)

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals ) Identifier:
First received: March 16, 2009
Last updated: November 25, 2015
Last verified: November 2015
There are no treatments specifically approved after recurrence or progression on a non steroidal aromatase inhibitors (NSAI). In light of the need for new treatment options for postmenopausal women after failure of prior NSAI therapy, the purpose of this Phase III study is to compare efficacy and safety of a treatment with exemestane + everolimus to exemestane + placebo in postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer refractory to NSAI.

Condition Intervention Phase
Breast Cancer
Drug: Everolimus
Drug: Exemestane
Drug: Everolimus Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blind, Placebo-Controlled Study of Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessments. [ Time Frame: date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first ,reported between day of first patient randomized, 27 July 2009, until cut-off date 11 February 2011. ] [ Designated as safety issue: No ]
    Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST 1.0). For patients with no target lesion, in the absence of new lesions, the overall lesion response at each assessment was one of following: Complete Response CR), Stable Disease SD), Unknown, or Progressive Disease (PD) based on non-target lesion responses. The following is considered progression among patients with lytic or mixed (lytic+sclerotic) bone lesions: appearance of ≥1 new lytic lesions in bone; the appearance of ≥ new lesions outside of bone and unequivocal progression of existing bone lesions.

Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Every 3 months after End of Treatment + 28 days (every 6 weeks before) ] [ Designated as safety issue: No ]
    Overall survival, the key secondary endpoint in this study, is defined as the time from date of randomization to the date of death due to any cause.

  • Overall Response Rate (ORR) [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
    ORR is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST.

  • Incidence of Adverse Events (AEs)/Serious Adverse Events (SAEs) [ Time Frame: Continuous and every 6 weeks ] [ Designated as safety issue: Yes ]
    In addition to AEs/SAEs, shift from baseline in vital signs and laboratory results (hematology, blood chemistry) will be reported.

  • Qol Scores ECOG Performance Status [ Time Frame: Every 6 weeks ] [ Designated as safety issue: Yes ]
    Change in QoL scores over time and time to deterioration of ECOG performance status.

  • Clinical Benefit Rate (CBR) [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
    CBR is defined as the proportion of patients whose best overall response is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks, according to RECIST.

Enrollment: 724
Study Start Date: June 2009
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus + Exemestane
Everolimus 10 mg daily in combination with exemestane 25 mg daily
Drug: Everolimus
Everolimus was formulated as tablets of 5-mg strength and was packaged into blister packs . Everolimus (two 5 mg tablets daily) were administered in a blinded manner on their respective treatment arms by continuous oral daily dosing.
Other Name: RAD001
Active Comparator: Placebo + Exemestane
Placebo of everolimus in combination with exemestane 25 mg daily
Drug: Exemestane
Exemestane 25 mg orally daily.
Drug: Everolimus Placebo
Placebo was formulated to be indistinguishable from the everolimus tablets. Matching placebo (two tablets daily) were administered in a blinded manner on their respective treatment arms by continuous oral daily dosing.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
  • Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
  • Postmenopausal women.
  • Disease refractory to non steroidal aromatase inhibitors (NSAI),
  • Radiological or clinical evidence of recurrence or progression on or after the last systemic therapy prior to randomization.
  • Patients must have at least one lesion that can be accurately measured or bone lesions in the absence of measurable disease as defined above.

Exclusion Criteria:

  • HER2-overexpressing patients
  • Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites etc.).
  • Patients who received more than one chemotherapy line for Advanced Breast Cancer.
  • Previous treatment with exemestane or mTOR inhibitors.
  • Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
  • Radiotherapy within four weeks prior to randomization
  • Currently receiving hormone replacement therapy,

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00863655

  Show 199 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):

Responsible Party: Novartis Pharmaceuticals Identifier: NCT00863655     History of Changes
Other Study ID Numbers: CRAD001Y2301  2008-008698-69 
Study First Received: March 16, 2009
Results First Received: July 31, 2012
Last Updated: November 25, 2015
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Agency for Health and Food Safety
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Brazil: National Health Surveillance Agency
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Egypt: Ministry of Health, Drug Policy and Planning Center
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy
Italy: National Institute of Health
Japan: Pharmaceuticals and Medical Devices Agency
Netherlands: Medicines Evaluation Board (MEB)
New Zealand: Food Safety Authority
Norway: Norwegian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Thailand: Food and Drug Administration
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Breast Cancer
Estrogen Receptor positive

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal processed this record on January 18, 2017