Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study
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Introduction Denosumab, a fully human anti-RANKL monoclonal antibody, reduces the incidence of skeletal-related events in patients with bone metastases from solid tumors. We present survival data for the subset of patients with lung cancer, participating in the phase 3 trial of denosumab versus zoledronic acid (ZA) in the treatment of bone metastases from solid tumors (except breast or prostate) or multiple myeloma.Methods Patients were randomized 1:1 to receive monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg. An exploratory analysis, using Kaplan-Meier estimates and proportional hazards models, was performed for overall survival among patients with non-small-cell lung cancer (NSCLC) and SCLC.Results Denosumab was associated with improved median overall survival versus ZA in 811 patients with any lung cancer (8.9 versus 7.7 months; hazard ratio [HR] 0.80) and in 702 patients with NSCLC (9.5 versus 8.0 months; HR 0.78) (p = 0.01, each comparison). Further analysis of NSCLC by histological type showed a median survival of 8.6 months for denosumab versus 6.4 months for ZA in patients with squamous cell carcinoma (HR 0.68; p = 0.035). Incidence of overall adverse events was balanced between treatment groups; serious adverse events occurred in 66.0% of denosumab-treated patients and 72.9% of ZA-treated patients. Cumulative incidence of osteonecrosis of the jaw was similar between groups (0.7% denosumab versus 0.8% ZA). Hypocalcemia rates were 8.6% with denosumab and 3.8% with ZA.Conclusion In this exploratory analysis, denosumab was associated with improved overall survival compared with ZA, in patients with metastatic lung cancer.
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In an exploratory analysis of a large phase III trial, denosumab was associated with improved median OS in a subgroup of 702 metastatic NSCLC patients.
“In an exploratory analysis of a large phase III trial, denosumab was associated with improved median OS in the subgroup of 702 metastatic NSCLC patients [162].”
From Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) · cites this paper as [162]
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- Authors
- Scagliotti, G. V., Hirsh, V., Siena, S., Henry, D. H., Woll, P. J., Manegold, C., Solal-Celigny, P., Rodriguez, G., Krzakowski, M., Mehta, N. D., Lipton, L., García-Sáenz, J. A., Pereira, J. R., Prabhash, K., Ciuleanu, T.-E., Kanarev, V., Wang, H., Balakumaran, A., & Jacobs, I.
- Affiliations
- University of Turin (IT)
- McGill University Health Centre (CA)
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
- Pennsylvania Hospital (US)
- Weston Park Cancer Centre (GB)
- Heidelberg University (DE)
- The Maria Sklodowska-Curie National Research Institute of Oncology (PL)
- Illinois CancerCare (US)
- Western Hospital (AU)
- Universidade de São Paulo (BR)
- Tata Memorial Hospital (IN)
- Institute of Oncology Prof. Dr. Ion Chiricuta (RO)
- Amgen (United States) (US)
- Corresponding author
- Scagliotti, Giorgio Vittorio
- ORCID
- Venue
- Journal of Thoracic Oncology
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 7
- Issue
- 12
- Pages
- 1823-1829
- ISSN
- 1556-0864 (ISSN-L)
- OpenAlex
- W2087769940
- Cited by
- 335
- References
- 25
- Citations by year
- 2026: 4 · 2025: 18 · 2024: 14 · 2023: 19 · 2022: 36 · 2021: 31 · 2020: 34 · 2019: 27 · 2018: 23 · 2017: 28 · 2016: 23 · 2015: 28 · 2014: 27 · 2013: 18 · 2012: 4
- FWCI
- 12.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thoracic Oncology (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- Amgen
- Eli Lilly and Company
- Pfizer
- Topics
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Surgery › Management of metastatic bone disease
- Keywords
- denosumab, zoledronic acid, bone metastasis, lung cancer, non-small cell lung cancer, small cell lung cancer, RANKL inhibition, overall survival, osteonecrosis of the jaw, hypocalcemia, skeletal-related events, squamous cell carcinoma
- MeSH terms
- Denosumab, Zoledronic Acid, Adenocarcinoma, Adolescent, Adult, Aged, Bone Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Diphosphonates, Double-Blind Method, Female, Follow-Up Studies, Humans, Imidazoles, International Agencies, Lung Neoplasms, Male, Middle Aged, Neoplasm Staging, Prognosis, Survival Rate, Bone Density Conservation Agents, RANK Ligand, Small Cell Lung Carcinoma, Young Adult, Antibodies, Monoclonal, Humanized
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