Last reviewed · How we verify

NCT00863655: BOLERO-2

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

Completed Phase 3 Results posted Last updated 2 May 2017
What this trial tests

Phase 3 trial testing Everolimus in Breast Cancer in 724 participants. Completed in 4 December 2014.

Timeline
3 June 2009
Primary endpoint
4 December 2014
4 December 2014

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment724
Start date3 June 2009
Primary completion4 December 2014
Estimated completion4 December 2014
Sites200 locations across Hong Kong, Italy, Japan, Poland, South Korea, New Zealand, Netherlands, Turkey (Türkiye)

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, female only, with Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessments. Primary · 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 up to about 19 months

Progression-free survival, the primary endpoint in this study, is defined as the time from the date of randomization to the date of first documented radiological progression or death due to any cause. Disease progression was based on the tumor assessment by the local radiologist or investigator using RECIST 1.0 criteria. If a patient did not progress or known to have died at the date of the analysis cut-off or start of another antineoplastic therapy, the PFS date was censored to the date of last adequate tumor assessment prior to cut-off date or start of antineoplastic therapy. For patients wi

GroupValue95% CI
Everolimus + Exemestane6.936.44 – 8.05
Placebo + Exemestane2.832.76 – 4.14
Overall Survival (OS) by Number of Deaths Secondary · up to 53 months

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. If a patient is not known to have died, survival was censored at the date of last contact.

GroupValue95% CI
Everolimus + Exemestane267
Placebo + Exemestane143
Overall Survival (OS) by Median Secondary · up to 53 months

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.

GroupValue95% CI
Everolimus + Exemestane30.9827.96 – 34.56
Placebo + Exemestane26.5522.57 – 33.08
Overall Response Rate (ORR) Secondary · up to 21 months

Overall response rate (ORR) is the percentage of patients with a best overall response of complete response (CR) or partial response (PR) according to RECIST 1.0. Per RECIST criteria 1.0, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.

GroupValue95% CI
Everolimus + Exemestane9.5
Placebo + Exemestane0.4
Clinical Benefit Rate (CBR) Secondary · up to 21 months

CBR is defined as the percentage of patients with best overall response of either complete response (CR), a partial response (PR) or stable disease (SD) \>= 24 weeks, according to RECIST 1.0. Per RECIST criteria 1.0, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; PD = At least a 20% increase in the sum of the longest diameter of all measured

GroupValue95% CI
Everolimus + Exemestane33.4
Placebo + Exemestane18.0
Proportion of Patients With no Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) Using Kaplan-Meier Secondary · 2, 4, 6, 9 months

The ECOG PS (Eastern Cooperative Oncology Group Performance Scale) is a standard criteria for measuring how treatment of cancer impacts level of functioning in terms of the ability to care for oneself, daily activity, \& physical ability (walking, working, etc.). Scale score ranges:0 to 5, 5 being the worst. Scale index: 0: Fully active, able to carry on all pre-disease performance without restriction. 1: Restricted in physically strenuous activity but ambulatory \& able to carry out work of a light or sedentary nature. 2: Ambulatory \& capable of all self-care but unable to carry out any work

2 Months
GroupValue95% CI
Everolimus + Exemestane0.840.80 – 0.87
Placebo + Exemestane0.870.82 – 0.91
4 Months
GroupValue95% CI
Everolimus + Exemestane0.740.70 – 0.78
Placebo + Exemestane0.800.73 – 0.85
6 Months
GroupValue95% CI
Everolimus + Exemestane0.640.58 – 0.69
Placebo + Exemestane0.670.57 – 0.75
9 Months
GroupValue95% CI
Everolimus + Exemestane0.570.50 – 0.63
Placebo + Exemestane0.470.32 – 0.61
Patient-reported Outcomes (PROs): Time to Deterioration of PRO Scores Using Kaplan Meier - EORTC QLQ-C30 Secondary · Up to 21 months

The QLQ-C30 is composed of both multi-item scales and single-item measures. These include 5 functional scales, 3 symptom scales, a global health status - QoL scale, and 6 single items. Each of the multi-item scales includes a different set of items - no item occurs in more than 1 scale. All of the scales measures range in score from 0 to 100. A high scale score = higher response level. Thus a high score for a functional scale represents a healthy level of function, a high score for the global health status / QoL represents a high quality of life but a high score for a symptom scale / item repr

Deterioration global health status score ≥ 5%
GroupValue95% CI
Everolimus + Exemestane4.534.17 – 5.68
Placebo + Exemestane4.403.58 – 5.85
Deterioration in PF domain score of ≥ 5%
GroupValue95% CI
Everolimus + Exemestane4.834.17 – 6.97
Placebo + Exemestane4.372.83 – 7.00
Deterioration in EF domain score of ≥ 5%
GroupValue95% CI
Everolimus + Exemestane6.935.55 – 8.41
Placebo + Exemestane6.934.17 – 7.36
Deterioration in SF domain score of ≥ 5%
GroupValue95% CI
Everolimus + Exemestane8.346.93 – 10.87
Placebo + Exemestane7.035.62 – NA
Proportion of Patients With Having no Overall Response Based on Investigator Assessment Secondary · 2, 4, 6, 9 months

overall response = complete response (CR) + partial response (PR) per RECIST 1.0 Time to overall response (CR or PR) based on investigator is the time between date of randomization/start of treatment until first documented response (CR or PR). This analysis included all patients/responders. Patients who did not achieve a confirmed PR or CR were censored at last adequate tumor assessment date when they did not progress. Per RECIST criteria 1.0, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the b

2 months
GroupValue95% CI
Everolimus + Exemestane0.960.94 – 0.98
Placebo + Exemestane1.000.97 – 1.00
4 months
GroupValue95% CI
Everolimus + Exemestane0.930.91 – 0.95
Placebo + Exemestane1.000.97 – 1.00
6 months
GroupValue95% CI
Everolimus + Exemestane0.920.89 – 0.94
Placebo + Exemestane1.000.97 – 1.00
9 months
GroupValue95% CI
Everolimus + Exemestane0.900.88 – 0.93
Placebo + Exemestane1.000.97 – 1.00
Duration of Response (Among Participants With Best Overall Response of CR or PR) Estimated Per Kaplan-Meier Secondary · 21 months

Duration of response of CR or PR based on investigator applies only to patients whose best overall response was CR or PR (RECIST 1.0). The start date was the date of first documented response (CR or PR) and the end date and censoring is defined the same as that for time to progression. Per RECIST criteria 1.0, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.

GroupValue95% CI
Everolimus + Exemestane8.215.55 – NA
Placebo + ExemestaneNANA – NA
Everolimus Concentrations at Week 4 Secondary · pre-dose, 2 hours post-dose

Characterize the pharmacokinetics (PK) of everolimus in combination with exemestane using Cmin (pre-dose) and C2h (post-dose) at week 4 in a small group of patients.

Pre-dose (Cmin) (n:22)
GroupValue95% CI
Everolimus + Exemestane16.04± 9.356
2 hours post-dose (C2h) (n:24)
GroupValue95% CI
Everolimus + Exemestane46.50± 17.954
Exemestane Concentrations at Week 4 Secondary · predose, 2 hours post-dose

Characterize the PK of exemestane in combination with or without everolimus using Cmin and C2h at week 4 in a small group of patients.

Pre-dose (Cmin) (n: 34, n: 22)
GroupValue95% CI
Everolimus + Exemestane0.631.00 – 1.00
Placebo + Exemestane0.43NA – NA
2 hours post-dose (C2h) (n: 39, n: 22)
GroupValue95% CI
Everolimus + Exemestane23.160.68 – 0.94
Placebo + Exemestane13.30NA – NA
Estradiol Plasma Concentrations Secondary · Baseline, Week 4

Compare estradiol concentrations from baseline to week 4 in both treatment arms.

Baseline (n: = 41, 14)
GroupValue95% CI
Everolimus + Exemestane5.621.00 – 1.00
Placebo + Exemestane4.09NA – NA
Week 4 (n: 38, 15)
GroupValue95% CI
Everolimus + Exemestane3.500.68 – 0.94
Placebo + Exemestane5.17NA – NA

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Everolimus + Exemestane
Serious: 158/482 (33%)
Deaths:
Placebo + Exemestane
Serious: 37/238 (16%)
Deaths:

Serious adverse events (374 terms)

ReactionSystemEverolimus + ExemestanePlacebo + Exemestane
PneumonitisRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PneumoniaInfections and infestations
DyspnoeaRespiratory, thoracic and mediastinal disorders
PneumoniaInfections and infestations
AnaemiaBlood and lymphatic system disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
General physical health deteriorationGeneral disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
AstheniaGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders
Renal failureRenal and urinary disorders
NauseaGastrointestinal disorders
HyperglycaemiaMetabolism and nutrition disorders
Renal failureRenal and urinary disorders
Other adverse events (111 terms — click to expand)

ReactionSystemEverolimus + ExemestanePlacebo + Exemestane
StomatitisGastrointestinal disorders
StomatitisGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
Decreased appetiteMetabolism and nutrition disorders
NauseaGastrointestinal disorders
Weight decreasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
Weight decreasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DysgeusiaNervous system disorders
HeadacheNervous system disorders
Oedema peripheralGeneral disorders
AnaemiaBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Oedema peripheralGeneral disorders
VomitingGastrointestinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
Back painMusculoskeletal and connective tissue disorders
VomitingGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
ConstipationGastrointestinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
AstheniaGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders

Most-reported serious reactions: Pneumonitis, Pneumonitis, Dyspnoea, Pneumonia, Dyspnoea, Pneumonia, Anaemia, Pulmonary embolism.

Data from ClinicalTrials.gov NCT00863655 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer.
    Baselga J, Campone M, Piccart M, Burris HA, et al · · 2012 · cited 2147× · PMID 22149876 · DOI 10.1056/nejmoa1109653
  2. Targeting mTOR for cancer therapy.
    Hua H, Kong Q, Zhang H, Wang J, et al · · 2019 · cited 678× · PMID 31277692 · DOI 10.1186/s13045-019-0754-1
  3. Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.
    Panwar V, Singh A, Bhatt M, Tonk RK, et al · · 2023 · cited 628× · PMID 37779156 · DOI 10.1038/s41392-023-01608-z
  4. PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?
    Peng Y, Wang Y, Zhou C, Mei W, et al · · 2022 · cited 446× · PMID 35402264 · DOI 10.3389/fonc.2022.819128
  5. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†.
    Piccart M, Hortobagyi GN, Campone M, Pritchard KI, et al · · 2014 · cited 428× · PMID 25231953 · DOI 10.1093/annonc/mdu456
  6. Prevalence of ESR1 Mutations in Cell-Free DNA and Outcomes in Metastatic Breast Cancer: A Secondary Analysis of the BOLERO-2 Clinical Trial.
    Chandarlapaty S, Chen D, He W, Sung P, et al · · 2016 · cited 405× · PMID 27532364 · DOI 10.1001/jamaoncol.2016.1279
  7. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis.
    Yardley DA, Noguchi S, Pritchard KI, Burris HA, et al · · 2013 · cited 392× · PMID 24158787 · DOI 10.1007/s12325-013-0060-1
  8. Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer.
    Ye F, Dewanjee S, Li Y, Jha NK, et al · · 2023 · cited 361× · PMID 37415164 · DOI 10.1186/s12943-023-01805-y

Verify or expand the search:

Other trials of Everolimus

Trials testing the same drug.

Other recruiting trials for Breast Cancer

Currently open trials in the same condition.

Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00863655.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing