Trial reportJournal of the National Cancer Institute2013
Effect of everolimus on bone marker levels and progressive disease in bone in BOLERO-2.
Trial report in Journal of the National Cancer Institute, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 98 citations in OpenAlex.
- Global and regional prevalence of osteoporosis in kidney transplant recipients: a systematic review and meta-analysis.Clinical and experimental medicine · 2025Pooled it
- The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review.Aging clinical and experimental research · 2022Pooled it
- Everolimus plus exemestane as first-line therapy in HR⁺, HER2⁻ advanced breast cancer in BOLERO-2.Breast cancer research and treatment · 2014Trial
- Branched‑chain amino acid metabolism and bone metabolism: Implications for osteoporosis pathogenesis and therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- Research Progress on Signaling Pathways in Breast Cancer Bone Metastasis.Oncology research · 2026Review
- Bone Effects of Anti-Cancer Treatments in 2024.Calcified tissue international · 2025Review
- Bone metastases from endocrine cancer: advances in diagnosis, treatment, and prevention.Frontiers in endocrinology · 2025Review
- The role of everolimus in malignant bone tumor therapy: Molecular mechanisms, preclinical evidence, and advances in clinical applications.Oncology reviews · 2025Review
- Cancer treatment-induced bone loss.The Korean journal of internal medicine · 2024Review
- Bone Loss after Solid Organ Transplantation: A Review of Organ-Specific Considerations.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- A Representative Clinical Course of Progression, with Molecular Insights, of Hormone Receptor-Positive, HER2-Negative Bone Metastatic Breast Cancer.International journal of molecular sciences · 2024Review
- The emerging role of osteoclasts in the treatment of bone metastases: rationale and recent clinical evidence.Frontiers in oncology · 2024Review
- A Comprehensive Review of Interventional Clinical Trials in Patients with Bone Metastases.OncoTargets and therapy · 2023Review
- Role of Exemestane in the Treatment of Estrogen-Receptor-Positive Breast Cancer: A Narrative Review of Recent Evidence.Advances in therapy · 2022Review
- Case Report: Everolimus reduced bone turnover markers but showed no clinical benefit in a patient with severe progressive osseous heteroplasia.Frontiers in pediatrics · 2022Article
- Crosstalk Between Senescent Bone Cells and the Bone Tissue Microenvironment Influences Bone Fragility During Chronological Age and in Diabetes.Frontiers in physiology · 2022Review
- Review
- Review
- Role of mTOR and VEGFR Inhibition in Prevention of Metastatic Tumor Growth in the Spine.Frontiers in oncology · 2020Article
- Role of Altered Metabolic Microenvironment in Osteolytic Metastasis.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundBreast Cancer Trials of Oral Everolimus 2 (BOLERO-2), a phase III study in postmenopausal women with estrogen receptor-positive breast cancer progressing despite nonsteroidal aromatase inhibitor therapy, showed statistically significant benefits with adding everolimus to exemestane. Moreover, in preclinical studies, mammalian target of rapamycin inhibition was associated with decreased osteoclast survival and activity. Exploratory analyses in BOLERO-2 evaluated the effect of everolimus on bone marker levels and progressive disease in bone.
methodsPatients were treated with exemestane (25mg/day) and randomized (2:1) to everolimus (10mg/day; combination) or placebo (exemestane only). Exploratory endpoints included changes in bone turnover marker levels vs baseline and progressive disease in bone, defined as unequivocal progression of a preexisting bone lesion or the appearance of a new bone lesion.
resultsBaseline disease characteristics were well balanced between arms (N = 724); baseline bisphosphonate use was not (43.9% combination vs 54.0% exemestane only). At a median of 18 months of follow-up, median progression-free survival (primary endpoint) was statistically significantly longer with the combination vs exemestane only (Cox proportional hazard ratio = 0.45, 95% confidence interval = 0.38 to 0.54; log-rank, 1-sided P < .0001). Bone marker levels at 6 and 12 weeks increased with exemestane only, as expected, but decreased with the combination. The cumulative incidence rate of progressive disease in bone was lower in the combination arm. Bone-related adverse events occurred with similar frequency in both arms (3.3% combination vs 4.2% exemestane only).
conclusionThese exploratory analyses suggest that everolimus has beneficial effects on bone turnover and progressive disease in bone in patients receiving exemestane for hormone receptor-positive breast cancer progressing during/after nonsteroidal aromatase inhibitor therapy.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.